36 results on '"Kotlan, B"'
Search Results
2. Defining the Critical Hurdles in Cancer Immunotherapy
- Author
-
Fox, BA, Schendel, D.J., Butterfield, L.H., Aamdal, S., Allison, J.P., Ascierto, P.A., Atkins, M.B., Bartunkova, J., Bergmann, L., Berinstein, N., Bonorino, C.C., Borden, E., Bramson, J.L., Britten, C.M., Cao, X., Carson, W.E., Chang, A.E., Characiejus, D., Choudhury, A.R., Coukos, G., de Gruijl, T.D., Dillman, R.O., Dolstra, H., Dranoff, G., Durrant, L.G., Finke, J.H., Galon, J., Gollob, J.A., Gouttefangeas, C., Grizzi, F., Guida, M., Hakansson, L., Hege, K., Herberman, R.B., Hodi, F.S., Hoos, A., Huber, C., Hwu, P., Imai, K., Jaffee, E.M., Janetzki, S., June, C.H., Kalinski, P., Kaufmann, H.L., Kawakami, K., Kawakami, Y., Keilholtz, U., Khleif, S.N., Kiessling, R., Kotlan, B., Kroemer, G., Lapointe, R., Levitsky, H.I., Lotze, M.T., Di Maio, M., Marschner, J.P., Mastrangelo, M.J., Masucci, G., Melero, I., Nelief, C., Murphy, W.J., Nelson, B., Nicolini, A., Nishimura, M.I., Odunsi, K., Ohashi, P.S., O'Donnell-Tormey, J., Old, L.J., Ottensmeier, C., Papamichail, M., Parmiani, G., Pawelec, G., Proietti, E., Qin, S., Rees, R., Ribas, A., Ridolfi, R., Ritter, G., Rivoltini, L., Romero, P.J., Salem, M.L., Scheper, R.J., Seliger, B., Sharma, P., Shiku, H., Singh-Jasuja, H., Song, W., Straten, P.T., Tahara, H., Tian, Z., van der Burg, S.H., von Hoegen, P., Wang, E., Welters, M.J., Winter, H., Withington, T., Wolchok, J.D., Xiao, W., Zitvogel, L., Zwierzina, H., Marincola, F.M., Gajewski, T.F., Wigginton, J.M., Disis, M.L.A., Fox, BA, Schendel, D.J., Butterfield, L.H., Aamdal, S., Allison, J.P., Ascierto, P.A., Atkins, M.B., Bartunkova, J., Bergmann, L., Berinstein, N., Bonorino, C.C., Borden, E., Bramson, J.L., Britten, C.M., Cao, X., Carson, W.E., Chang, A.E., Characiejus, D., Choudhury, A.R., Coukos, G., de Gruijl, T.D., Dillman, R.O., Dolstra, H., Dranoff, G., Durrant, L.G., Finke, J.H., Galon, J., Gollob, J.A., Gouttefangeas, C., Grizzi, F., Guida, M., Hakansson, L., Hege, K., Herberman, R.B., Hodi, F.S., Hoos, A., Huber, C., Hwu, P., Imai, K., Jaffee, E.M., Janetzki, S., June, C.H., Kalinski, P., Kaufmann, H.L., Kawakami, K., Kawakami, Y., Keilholtz, U., Khleif, S.N., Kiessling, R., Kotlan, B., Kroemer, G., Lapointe, R., Levitsky, H.I., Lotze, M.T., Di Maio, M., Marschner, J.P., Mastrangelo, M.J., Masucci, G., Melero, I., Nelief, C., Murphy, W.J., Nelson, B., Nicolini, A., Nishimura, M.I., Odunsi, K., Ohashi, P.S., O'Donnell-Tormey, J., Old, L.J., Ottensmeier, C., Papamichail, M., Parmiani, G., Pawelec, G., Proietti, E., Qin, S., Rees, R., Ribas, A., Ridolfi, R., Ritter, G., Rivoltini, L., Romero, P.J., Salem, M.L., Scheper, R.J., Seliger, B., Sharma, P., Shiku, H., Singh-Jasuja, H., Song, W., Straten, P.T., Tahara, H., Tian, Z., van der Burg, S.H., von Hoegen, P., Wang, E., Welters, M.J., Winter, H., Withington, T., Wolchok, J.D., Xiao, W., Zitvogel, L., Zwierzina, H., Marincola, F.M., Gajewski, T.F., Wigginton, J.M., and Disis, M.L.A.
- Abstract
Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. © 2011 Fox et al; licensee BioMed Central Ltd.
- Published
- 2011
- Full Text
- View/download PDF
3. Immunoglobulin repertoire of B lymphocytes infiltrating breast medullary carcinoma
- Author
-
Kotlan, B., primary, Simsa, P., additional, Foldi, J., additional, Fridman, W.H., additional, Glassy, M., additional, Mc Knight, M., additional, and Teillaud, JL, additional
- Published
- 2004
- Full Text
- View/download PDF
4. High anti-paternal cytotoxic T-lymphocyte precursor frequencies in women with unexplained recurrent spontaneous abortions
- Author
-
Kotlan, B., primary
- Published
- 2001
- Full Text
- View/download PDF
5. A scFv Phage Display Mini Library Generated from the Immunoglobulin Repertoire of Breast Medullary Carcinoma Infiltrating B Lymphocytes
- Author
-
Kotlan, B., primary, Simsa, P., additional, Gruel, N., additional, Foldi, J., additional, Fridman, W. H., additional, Petranyi, G., additional, and Teillaud, J. L., additional
- Published
- 2000
- Full Text
- View/download PDF
6. Immunoglobulin repertoire of B lymphocytes infiltrating breast medullary carcinoma.
- Author
-
Kotlan, B., Simsa, P., Foldi, J., Fridman, W. H., Glassy, M., Mc Knight, M., and Teillaud, J. L.
- Subjects
- *
IMMUNOGLOBULINS , *BREAST cancer , *LYMPHOCYTES , *TUMORS , *DNA , *PROGNOSIS - Abstract
Tumor specific peptides recognized by T lymphocytes infiltrating solid tumors, as well as the corresponding T cell receptor (TcR) repertoire usage, have been extensively investigated. By contrast, tumor infiltrating B cells and their immunoglobulin (Ig) repertoire have been studied only in a limited number of tumors. The objective of the present study was to determine, whether DNA sequence analysis of the expressed immunoglobulin variable regions of B cells that infiltrate breast cancer, could be used to reveal a potential specific tumor binding capacity of the antibodies. To answer this question, about 200 expressed Ig heavy (VH) and light chain variable gene (VL) regions were cloned, sequenced and comparatively analysed from a typical medullary beast carcinoma (MBC), where the massive B and plasma cell infiltration correlates with favourable prognosis despite of its high grade. The tumor infiltrating B cell Ig heavy and light chain sequences could be classified into clusters, families and subgroups, based on the identity level to germline, showing a pattern of oligoclonality. Some overrepresented clusters could be determined. In the course of a detailed analysis and search in Blastn database, a number of VH and VL sequences showed more than 99% homology to DNA sequences of Ig VH region, with proved tumor antigen binding capacity. Our data suggest, that potential tumor binder Ig VH and VL sequences might be selected using a detailed immunoglobulin variable region analysis. This new approach might have a benefit for further antibody engineering, as difficulties in search for tumor binders by phage library selection might be reduced and the time for selection shortened. [ABSTRACT FROM AUTHOR]
- Published
- 2003
7. The significance of blocking antibodies in the monitoring of immunotherapy in immune abortions
- Author
-
Fülöp, V., Padányi, A., Simsa, P., Kotlán, B., Rajczy, K., Jakab, J., Hoffer, I., Hriczko, J., Toth, A., and Petrányi, Gy.
- Published
- 2010
- Full Text
- View/download PDF
8. In-vitro and in-vivo studies on the induction of neopterin biosynthesis by cytokines, alloantigens and lipopolysaccharide (LPS).
- Author
-
Troppmair, J., Nachbaur, K., Herold, M., Aulitzky, W., Tilg, H., Gastl, G., Bieling, P, Kotlan, B., Flener, R., Mull, B., Aulitzky, W. O., Rokos, H., and Huber, Ch.
- Subjects
BIOMARKERS ,IMMUNE response ,CYTOKINES ,BLOOD plasma ,BIOSYNTHESIS ,NEOPTERIN - Abstract
Recently we presented evidence that cellular immune responses are associated with increased in-vitro and in-vivo excretion of neopterin (Huber el al. 1983) and that, in vitro at least, macrophages and IFN-γ play a key role in the induction of this phenomenon (Huber et al., 1984). Although this marker is increasingly applied for monitoring of human disease, there is limited knowledge about the mechanism(s) responsible for its increased biosynthesis during inflammatory states. To further elucidate this question we evaluated neopterin and IFN-levels in culture supernatants of human blood cells and in patients' sera. Cells or patients were exposed to a panel of recombinant cytokines. alloantigens or lipopolysaccharide. To investigate indirect stimulation by induction of production of endogenous IFNs, the impact of neutralization of IFNs by addition of specific antibodies was also studied. The data confirm our previous results which identified the monocyte/macrophage as the main producer ceil among human blood cells. They further demonstrate that, at least in vitro. IFN-γ, IFN-α and LPS can all stimulate neopterin release independently from each other. Thirdly, they indicate that stimuli such as alloantigens or TNF-α can indirectly enhance neopterin release by their capacity to induce production of endogenous IFN-γ. On the basis of these data we conclude that enhanced neopterin biosynthesis does not necessarily relate to activation of T cells but can also be caused by non-immune stimuli. [ABSTRACT FROM AUTHOR]
- Published
- 1988
9. Immunoglobulin variable regions usage by B-lymphocytes infiltrating a human breast medullary carcinoma
- Author
-
Kotlan, B., Gruel, N., Zafrani, B., Furedi, G., Foldi, J., Petranyi, G. G., Fridman, W. H., and Teillaud, J.-L.
- Published
- 1999
- Full Text
- View/download PDF
10. Immunoglobulin repertoire of B lymphocytes infiltrating breast medullary carcinoma
- Author
-
Kotlan B, Simsa P, Foldi J, Wh, Fridman, Glassy M, McKnight M, and Jean-Luc Teillaud
- Subjects
B-Lymphocytes ,Lymphocytes, Tumor-Infiltrating ,Genes, Immunoglobulin ,Carcinoma, Medullary ,Immunoglobulin Variable Region ,Humans ,Breast Neoplasms ,Female ,Immunoglobulin Light Chains ,Sequence Analysis, DNA ,Immunoglobulin Heavy Chains - Abstract
Tumor specific peptides recognized by T lymphocytes infiltrating solid tumors, as well as the corresponding T cell receptor (TcR) repertoire usage, have been extensively investigated. By contrast, tumor infiltrating B cells and their immunoglobulin (Ig) repertoire have been studied only in a limited number of tumors. The objective of the present study was to determine, whether DNA sequence analysis of the expressed immunoglobulin variable regions of B cells that infiltrate breast cancer, could be used to reveal a potential specific tumor binding capacity of the antibodies. To answer this question, about 200 expressed Ig heavy (VH) and light chain variable gene (VL) regions were cloned, sequenced and comparatively analysed from a typical medullary beast carcinoma (MBC), where the massive B and plasma cell infiltration correlates with favourable prognosis despite of its high grade. The tumor infiltrating B cell Ig heavy and light chain sequences could be classified into clusters, families and subgroups, based on the identity level to germline, showing a pattern of oligoclonality. Some overrepresented clusters could be determined. In the course of a detailed analysis and search in Blastn database, a number of VH and VL sequences showed more than 99% homology to DNA sequences of Ig VH region, with proved tumor antigen binding capacity. Our data suggest, that potential tumor binder Ig VH and VL sequences might be selected using a detailed immunoglobulin variable region analysis. This new approach might have a benefit for further antibody engineering, as difficulties in search for tumor binders by phage library selection might be reduced and the time for selection shortened.
11. Cytokines in the Control of Beta-2 Microglobulin Release. I. In vitro Studies on Various Haemopoietic Cells
- Author
-
Nachbaur, K., primary, Troppmair, J., additional, Bieling, P., additional, Kotlan, B., additional, König, P., additional, and Huber, C.H., additional
- Published
- 1988
- Full Text
- View/download PDF
12. Cytokines in the Control of Beta-2 Microglobulin Release. II. In vivo Studies with Recombinant Interferons and Antigens
- Author
-
Nachbaur, K., primary, Troppmair, J., additional, Kotlan, B., additional, König, P., additional, Aulitzky, W., additional, Bieling, P., additional, and Huber, C.H., additional
- Published
- 1988
- Full Text
- View/download PDF
13. Specific immune dysfunction in recurrent spontaneous abortion, extreme high CTLp frequencies, lack of serum blocking lgG, shared TLX/MCP/CD46 phenotypes
- Author
-
Kotlán, B., Padányi, Å., Petrányi, Gy.G., Gyódi, É., and Szigetvári, M.
- Published
- 1994
- Full Text
- View/download PDF
14. P460 - The association of cytotoxic T-lymphocyte precursor cell frequency with acute and chronic GVHD in matched sibling bone marrow transplantation
- Author
-
Kotlán, B., Dénes, R, Gyódi, É., Sipos, A., Pócsik, É., Torbáqyi, É., Bátai, Á., Barta, A., Masszi, T., Poros, A., Pálóczi, K., and Gy, G.
- Published
- 1996
- Full Text
- View/download PDF
15. P444 - Unrelated BMT in Hungary, 4 years experience
- Author
-
Gyódi, É., Nyán, E., Kotlán, B., Rajczy, K., Pénzes, M., Dénes, R., Masszi, T., Tímár, L., and Petrányi, Gy.
- Published
- 1996
- Full Text
- View/download PDF
16. Immunoglobulin variable regions usage by B lymphocytes infiltrating human breast medullary carcinoma
- Author
-
Kotlán, B., Gruel, N., Zafrani, B., Földi, J., Petrányi, Gy.G., Fridman, W.H., and Teillaud, Jean-Luc
- Published
- 1997
- Full Text
- View/download PDF
17. Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume II-practical challenges.
- Author
-
Cesano A, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells DK, Wyant TL, and Rutella S
- Subjects
- Disease Progression, Humans, Biomarkers, Tumor metabolism, Immunotherapy methods
- Abstract
The development of strongly predictive validated biomarkers is essential for the field of immuno-oncology (IO) to advance. The highly complex, multifactorial data sets required to develop these biomarkers necessitate effective, responsible data-sharing efforts in order to maximize the scientific knowledge and utility gained from their collection. While the sharing of clinical- and safety-related trial data has already been streamlined to a large extent, the sharing of biomarker-aimed clinical trial derived data and data sets has been met with a number of hurdles that have impaired the progression of biomarkers from hypothesis to clinical use. These hurdles include technical challenges associated with the infrastructure, technology, workforce, and sustainability required for clinical biomarker data sharing. To provide guidance and assist in the navigation of these challenges, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to outline the challenges that researchers currently face, both at the conceptual level (Volume I) and at the technical level (Volume II). The committee also suggests possible solutions to these problems in the form of professional standards and harmonized requirements for data sharing, assisting in continued progress toward effective, clinically relevant biomarkers in the IO setting., Competing Interests: Competing interests: AC—Employee: ESSA Pharma; Consulting fees: Refuge Bio, Arch Oncology, Qognit, Nanostring. MAC—Employee: Roche Diagnostic GMBH; Stakeholder: Roche; Patent: 10878NDR. SG—Consultancy/advisory fees: Merck, NeonTherapeutics, OncoMed; Research funding: Agenus, Bristol-Myers Squibb, Genentech, Immune Design, Janssen R&D, Pfizer, Regeneron, Takeda. BG—Employee: Hoffmann La Roche; Stockholder: Roche. VK—Employee: Hoffmann La Roche; Stockholder: Roche; Patent: EP3221355A1. JMK—Grant funding: Prometheus, Merck; Personal fees: Array Biopharma, Bristol-Myers Squibb, Novartis, Roche; Grants and personal fees: Immunocore. EM—Director/shareholder: CancerProbe Pty Ltd. AN—Consulting fees: CytomX Therapeutics, Novartis, Kymab, Genome; Contracted research: National Cancer Institute, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, ARMO Biosciences, Eli Lilly, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Kymab, PsiOxus; Travel accommodation: ARMO Biosciences; Partner contracted research: Immune Deficiency Foundation. DKW—Scientific co-founder, equity holder, and paid advisor: Immunai. TLW—Employee/stockholder: Biolojic Design. JG, MK, BK, GVM, AM, SR, VT, NT, and EW—Nothing to disclose. SITC Staff: AK, BL, LL, and SMW—Nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
18. Society for Immunotherapy of Cancer clinical and biomarkers data sharing resource document: Volume I-conceptual challenges.
- Author
-
Rutella S, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells DK, Wyant TL, and Cesano A
- Subjects
- Humans, Biomarkers, Tumor metabolism, Immunotherapy methods, Information Dissemination methods
- Abstract
The sharing of clinical trial data and biomarker data sets among the scientific community, whether the data originates from pharmaceutical companies or academic institutions, is of critical importance to enable the development of new and improved cancer immunotherapy modalities. Through data sharing, a better understanding of current therapies in terms of their efficacy, safety and biomarker data profiles can be achieved. However, the sharing of these data sets involves a number of stakeholder groups including patients, researchers, private industry, scientific journals and professional societies. Each of these stakeholder groups has differing interests in the use and sharing of clinical trial and biomarker data, and the conflicts caused by these differing interests represent significant obstacles to effective, widespread sharing of data. Thus, the Society for Immunotherapy of Cancer (SITC) Biomarkers Committee convened to identify the current barriers to biomarker data sharing in immuno-oncology (IO) and to help in establishing professional standards for the responsible sharing of clinical trial data. The conclusions of the committee are described in two position papers: Volume I-conceptual challenges and Volume II-practical challenges, the first of which is presented in this manuscript. Additionally, the committee suggests actions by key stakeholders in the field (including organizations and professional societies) as the best path forward, encouraging the cultural shift needed to ensure responsible data sharing in the IO research setting., Competing Interests: Competing interests: AC—Employee: ESSA Pharma; Consulting fees: Refuge Bio, Arch Oncology, Qognit, Nanostring. BG—Employee: Hoffmann La Roche; Stockholder: Roche. MAC—Employee: Roche Diagnostic GMBH; Stakeholder: Roche; Patent: 10878NDR. SG—Consultancy/Advisory Fees: Merck, Neon Therapeutics, OncoMed; Research Funding: Agenus, Bristol-Myers Squibb, Genentech, Immune Design, Janssen R&D, Pfizer, Regeneron, Takeda. JMK—Grant Funding: Prometheus, Merck; Personal Fees: Array Biopharma, Bristol-Myers Squibb, Novartis, Roche; Grants and Personal Fees: Immunocore. EM—Director/Shareholder: CancerProbe Pty Ltd. VK—Employee: Hoffmann La Roche; Stockholder: Roche; Patent: EP3221355A1. AN—Consulting Fees: CytomX Therapeutics, Novartis, Kymab, Genome; Contracted Research: National Cancer Institute, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, ARMO Biosciences, Eli Lilly, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Kymab, PsiOxus; Travel Accommodation: ARMO Biosciences; Partner Contracted Research: Immune Deficiency Foundation. TLW—Employee/Stockholder: Biolojic Design. DKW is a scientific co-founder, equity holder and paid advisor to Immunai. SR, JG, BK, MK, AM, GVM, VT, NT, and EW have nothing to disclose. SITC Staff: AK, BL, LL, and SMW have nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
- Full Text
- View/download PDF
19. Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor.
- Author
-
Kotlan B, Horvath S, Eles K, Plotar VK, Naszados G, Czirbesz K, Blank M, Farkas E, Toth L, Tovari J, Szekacs A, Shoenfeld Y, Godeny M, Kasler M, and Liszkay G
- Subjects
- Cell Line, Tumor, Humans, B-Lymphocytes immunology, Breast Neoplasms immunology, Gangliosides immunology, Lymphocytes, Tumor-Infiltrating immunology, Melanoma immunology, Single-Chain Antibodies immunology
- Abstract
There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy.
- Published
- 2019
- Full Text
- View/download PDF
20. Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.
- Author
-
Kotlan B, Plotar V, Eles K, Horvath S, Balatoni T, Csuka O, Újhelyi M, Sávolt Á, Szollar A, Vamosi-Nagy I, Toth L, Farkas E, Toth J, Kasler M, and Liszkay G
- Abstract
Aim of the Study: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells., Materials and Methods: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized., Results: We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology., Conclusions: We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
- Full Text
- View/download PDF
21. [Genetic information from tumor-infiltrating B lymphocytes as a driver tool ("GPS") for anti-tumor T cell CARs].
- Author
-
Kotlan B, Csuka O, Tóth L, Farkas E, Plótár V, Horváth S, Éles K, Olasz J, Tóth J, Kásler M, and Liszkay G
- Subjects
- B-Lymphocytes immunology, B-Lymphocytes metabolism, Humans, Lymphocytes, Tumor-Infiltrating, T-Lymphocytes immunology, T-Lymphocytes metabolism, Genetic Therapy methods, Neoplasms immunology, Receptors, Antigen, B-Cell metabolism, Receptors, Antigen, T-Cell metabolism
- Abstract
The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity. DNA sequences of these antibody variable regions were subjects to get engineered into new CAR constructs. Our novel strategy harnesses tumor-infiltrating B cells' unique capacity to reveal highly tumor-associated disialylated glycosphingolipids (GD3 gangliosides). We used these human antibody fragments for generating GD3 ganglioside specific CAR gene constructs for potential usage in solid tumors.
- Published
- 2016
22. The novel panel assay to define tumor-associated antigen-binding antibodies in patients with metastatic melanomas may have diagnostic value.
- Author
-
Kotlan B, Liszkay G, Blank M, Csuka O, Balatoni T, Toth L, Eles K, Horvath S, Naszados G, Olasz J, Banky B, Toth J, Godeny M, Marincola FM, Kasler M, and Shoenfeld Y
- Subjects
- Antibodies, Neoplasm blood, Antibodies, Neoplasm isolation & purification, Antibody Formation, Antibody Specificity immunology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Biomarkers, Cell Line, Transformed, Cell Line, Tumor, Cell Proliferation, Flow Cytometry, Humans, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Melanoma blood, Neoplasm Metastasis, Tumor Microenvironment immunology, Antibodies, Neoplasm immunology, Antigens, Neoplasm immunology, Melanoma immunology, Melanoma pathology
- Abstract
We aim to harness the natural humoral immune response by various technologies to get novel biomarkers. A complex antibody analysis in sera and in the tumor microenvironment leads to reveal tumor-specific antibodies. More strategies were introduced to select the most effective one to identify potential tumor antigen-binding capacity of the host. Epstein-Barr virus transformation and cloning with limiting dilution assay, magnetic cell sorting and antibody phage display with further methodological improvements were used in epithelial and neuroectodermal cancers. Column-purified sera of patient with melanoma were tested by immunofluorescence assay, while sera of further melanoma patients were processed for membrane-binding enzyme-linked immunosorbent assay. Some supernatants of selected B cell clones and purified antibodies showed considerable cancer cell binding capacity by immunofluorescence FACS analysis and confocal laser microscopy. Our native tumor cell membrane preparations helped to test soluble scFv and patients' sera for tumor binder antibodies. A complex tumor immunological study was introduced for patients with melanoma (ethical permission: ETT TUKEB 16462-02/2010); peripheral blood (n = 57) and surgically removed primary or metastatic tumors (n = 44) were gathered and processed at cellular immunological level. The technological developments proved to be important steps forward to the next antibody profile analyses at DNA sequence level. Cancer cell binding of patient-derived antibodies and natural immunoglobulin preparations of pooled plasma product intravenous immunoglobulins support the importance of natural human antibodies. Important cancer diagnostics and novel anticancer strategies are going to be built on these tools.
- Published
- 2015
- Full Text
- View/download PDF
23. Conference overview: Cancer Immunotherapy and Immunomonitoring (CITIM): moving forward.
- Author
-
Malyguine A, Umansky V, Kotlan B, Aptsiauri N, and Shurin MR
- Subjects
- Animals, Congresses as Topic, Europe, Eastern, Humans, Immunologic Surveillance, Immunotherapy methods, Monitoring, Physiologic methods, Neoplasms immunology, Neoplasms therapy
- Abstract
The immune system is a critical element involved in the control of tumor development and progression. While professionals have learned how to manipulate the immune system to generate tumor-specific immune responses, cancer immunotherapy has not yet delivered substantial clinical benefits. It has become increasingly clear that tumor-induced abnormalities in the immune system not only hamper tumor immunosurveillance, but also limit the efficacy of cancer immunotherapy. Meanwhile, the results of recent studies allow the belief that one is on the edge of a real breakthrough in this promising direction in cancer therapy. The 2(nd) International Conference 'Cancer Immunotherapy and Immunomonitoring (CITIM)' was the second meeting in Eastern Europe to specifically focus on the issue of immune regulation in the tumor environment, cancer immunotherapy, and immunomonitoring of immunotherapeutic clinical trials. This CITIM Conference held in Budapest, Hungary, was comprised from 12 plenary sessions, Best Abstract Award session, Poster session, and four Keynote lectures. Outstanding presentations and numerous productive discussions summarized the current place of the field and opened new directions for improving monitoring and therapy for patients with cancer.
- Published
- 2012
- Full Text
- View/download PDF
24. From cell regulation to patient survival: 2nd Cancer Immunotherapy and Immunomonitoring (CITIM) meeting, Budapest, 2-5 May 2011.
- Author
-
Umansky V, Malyguine A, Kotlan B, Aptsiauri N, and Shurin MR
- Subjects
- Animals, Gene Expression Regulation, Neoplastic immunology, Humans, Hungary, International Cooperation, Monitoring, Physiologic, Translational Research, Biomedical, Immunotherapy, Monitoring, Immunologic trends, Neoplasms immunology, Neoplasms therapy
- Published
- 2012
- Full Text
- View/download PDF
25. Defining the critical hurdles in cancer immunotherapy.
- Author
-
Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E, Bramson JL, Britten CM, Cao X, Carson WE, Chang AE, Characiejus D, Choudhury AR, Coukos G, de Gruijl T, Dillman RO, Dolstra H, Dranoff G, Durrant LG, Finke JH, Galon J, Gollob JA, Gouttefangeas C, Grizzi F, Guida M, Håkansson L, Hege K, Herberman RB, Hodi FS, Hoos A, Huber C, Hwu P, Imai K, Jaffee EM, Janetzki S, June CH, Kalinski P, Kaufman HL, Kawakami K, Kawakami Y, Keilholtz U, Khleif SN, Kiessling R, Kotlan B, Kroemer G, Lapointe R, Levitsky HI, Lotze MT, Maccalli C, Maio M, Marschner JP, Mastrangelo MJ, Masucci G, Melero I, Melief C, Murphy WJ, Nelson B, Nicolini A, Nishimura MI, Odunsi K, Ohashi PS, O'Donnell-Tormey J, Old LJ, Ottensmeier C, Papamichail M, Parmiani G, Pawelec G, Proietti E, Qin S, Rees R, Ribas A, Ridolfi R, Ritter G, Rivoltini L, Romero PJ, Salem ML, Scheper RJ, Seliger B, Sharma P, Shiku H, Singh-Jasuja H, Song W, Straten PT, Tahara H, Tian Z, van Der Burg SH, von Hoegen P, Wang E, Welters MJ, Winter H, Withington T, Wolchok JD, Xiao W, Zitvogel L, Zwierzina H, Marincola FM, Gajewski TF, Wigginton JM, and Disis ML
- Subjects
- Humans, International Cooperation, Translational Research, Biomedical, Immunotherapy, Neoplasms therapy
- Abstract
Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.
- Published
- 2011
- Full Text
- View/download PDF
26. Conference Scene: Immunotherapy reaches new milestones in cancer eradication.
- Author
-
Kotlan B, Umansky V, Malyguine AM, Marincola FM, and Shurin MR
- Subjects
- Animals, Clinical Trials as Topic, Congresses as Topic, Drug Approval, Evidence-Based Medicine, Humans, Hungary, Information Dissemination, Monitoring, Immunologic trends, Neoplasms pathology, Neoplasms therapy, Immunotherapy trends, Neoplasms immunology, Translational Research, Biomedical
- Abstract
Biotherapy is widely considered as the fourth treatment modality for patients with cancer, and uses the constantly increasing knowledge in molecular biology, cell biology and immunology. Biotherapy uses naturally occurring biological molecules (e.g., cytokines and antibodies) or works by the manipulation of normal biological mechanisms (controlling or inhibiting tumor growth). Important achievements in anticancer drug development are immunotherapeutic strategies recently approved by the US FDA as well as clinical data of the cancer patients treated in clinical trials. There is a need to expand these novel cancer immunotherapeutic modalities for cancer patients all over the world. To meet that goal, it is essential to spread the information, to summarize the new clinical data and to draw the conclusions from the clinical and preclinical investigations. These frontline tasks can be well advanced by organizing international conferences in this domain in less scientifically developed countries, with a significant tumor burden statistics. Therefore, special efforts were done to organize the 2nd International Cancer Immunotherapy and Immunomonitoring Conference (CITIM-2011) in Hungary.
- Published
- 2011
- Full Text
- View/download PDF
27. Pioneering the trail of cancer immunotherapy.
- Author
-
Kotlan B and Balwit JM
- Subjects
- Antibodies, Monoclonal therapeutic use, Humans, Immunotherapy, Neoplasms therapy
- Abstract
The annual conference of the International Society for Biological Therapy of Cancer (iSBTc), recently renamed the Society for Immunotherapy of Cancer (SITC), provides clinicians and scientists with a uniquely broad yet focused view of the growing field of tumor immunology and cancer immunotherapy. In this time of exciting new developments in cancer immunotherapy, it is critically important to effectively guide new immune-based advances from bench to bedside to improve outcomes of patients with cancer. iSBTc/SITC with its dedicated leadership (past and present) provides this guidance through its Annual Meeting and associated programs. This year the society celebrated its 25th Anniversary in Hyatt Regency Washington on Capitol Hill (Washington DC, USA), with educational offerings from 30 September to 4 October 2010.
- Published
- 2011
- Full Text
- View/download PDF
28. 15th International Conference on Human Antibodies and Hybridomas. 14-16 April 2010, Tiara Park Atlantico Hotel, Porto, Portugal.
- Author
-
Kotlan B
- Subjects
- Animals, Animals, Genetically Modified, Antineoplastic Agents therapeutic use, Communicable Diseases immunology, Humans, Hybridomas, Neoplasms immunology, Rats, Antibodies, Monoclonal therapeutic use, Communicable Diseases therapy, Neoplasms therapy
- Abstract
Antibodies and antibody conjugates are currently one of the largest classes of new drug entities under development. These versatile molecules are being investigated for the treatment of many pathological conditions, such as cancer and infectious, inflammatory and autoimmune diseases. Antibodies can exert biological effects as naked antibodies by themselves, or can be used as delivery agents conjugated with various drugs (e.g., immunoconjugates) and as tools of multistep targeting. Site-specific delivery of therapeutic agents has been the ultimate goal of the pharmaceutical industry, as it has the potential to maximize drug efficiency while minimizing side effects. Antibodies have much potential for this objective. Thus, it is useful to summarize some of the main strategies currently being employed for the development of these diverse therapeutic molecules and to highlight the recent novelties in the field. These goals were the focus of the 15th International Conference on Human Antibodies and Hybridomas, held during 14-16 April 2010 in Porto, Portugal.
- Published
- 2010
- Full Text
- View/download PDF
29. Intravenous immunoglobulin-based immunotherapy: an arsenal of possibilities for patients and science.
- Author
-
Kotlan B, Stroncek DF, and Marincola FM
- Subjects
- Abortion, Habitual immunology, Animals, Female, Humans, Immunomodulation, Neoplasms immunology, Pregnancy, Translational Research, Biomedical, Abortion, Habitual drug therapy, Immunoglobulins, Intravenous therapeutic use, Immunotherapy, Neoplasms drug therapy
- Abstract
The use of intravenous immunoglobulin (IVIG) concentrated from pooled healthy donors' plasma has gained increasing popularity. IVIG therapy has become important as a replacement therapy in primary and acquired humoral immunodeficiencies, and it has been extended to autoimmune, neurodegenerative and inflammatory conditions and transplantation therapy. Recurrent pregnancy failure and cancer are rather new platforms, where IVIG has shown its beneficial effects. This manuscript is focused on these two off-labelled usages. The immunomodulatory mechanisms of IVIG therapy appear as a coordinated orchestration of different functions, resulting in a synergistic effect. Treatment monitoring and detailed molecular analyses reveal how such treatments may interfere with disease pathogenesis. These finding may foster the development of novel therapeutic and/or preventive strategies. Studying this field with bidirectional bench-to-bedside and bedside-to-bench approaches fit well into 'the two-way road' paradigm of translational medicine.
- Published
- 2009
- Full Text
- View/download PDF
30. Turning laboratory findings into therapy: a marathon goal that has to be reached.
- Author
-
Kotlan B, Stroncek DF, and Marincola FM
- Subjects
- Biomedical Research trends, Chemistry, Clinical trends, Evidence-Based Medicine trends, Humans, Interdisciplinary Communication, Pharmaceutical Preparations, Research Design, Biomedical Research organization & administration, Chemistry, Clinical organization & administration, Evidence-Based Medicine organization & administration
- Abstract
The mission of translational research involves difficult tasks to be accomplished for its ultimate goal, i.e., the introduction of novel, effective therapeutic strategies in the clinic to diminish human suffering and cure life-threatening diseases. Translational research (also referred to as translational medicine) facilitates the translation of investment in biomedical research into successful medical treatment. This includes the transfer of diagnostic and therapeutic advances by proving their efficacy in large evidence-based trials. Through the study of humans novel insights about disease are brought back to the laboratory to identify new, observation-based strategies. This "two-way road" ("bench to bedside and bedside to bench") process includes formulating guidelines for drug development and principles for new therapeutic strategies; initiating clinical investigations that provide the biological basis for new therapies, and related clinical trials; defining therapeutic targets and clinical endpoints. It requires a systematic approach beginning with specimen sampling, patient data collection, laboratory investigations, data analysis, preclinical testing, clinical trials, treatment efficacy monitoring, and finally the evaluation of therapeutic result. The marathon well symbolizes the enormous efforts undertaken by clinicians, scientists, regulators, ethicists, patient advocates, drug developers, and others, coordinately attempting to overcome obstacles along this road toward the final "marathon goal in medicine".
- Published
- 2009
31. Antibody phage display: overview of a powerful technology that has quickly translated to the clinic.
- Author
-
Kotlan B and Glassy MC
- Subjects
- Drug Discovery, Genetic Vectors, Humans, Recombinant Fusion Proteins isolation & purification, Antibodies, Monoclonal genetics, Bacteriophages genetics, Biotechnology trends, Peptide Library, Recombinant Fusion Proteins genetics
- Abstract
Antibody-based immunologic reagents are useful for identifying, isolating, or eliminating cells with particular characteristics related to different diseases. Phage display is a highly valuable technique for antibody selection related to this purpose. In brief, a diverse group of antibody genes prepared from a patient or generated in vitro are inserted into a phagemid vector or the phage genome so that when the protein is expressed, it becomes anchored on the surface of the phage by fusion to a coat protein. A diverse library of recombinant antibodies is generated in this way and can then be exposed or panned on the antigen of interest, typically, this being a molecule associated with a particular pathological condition. Phage that carry proteins or peptides bind preferentially to the target and can thus be isolated from the library. The viruses that are recovered in this way also carry the gene for the binding moiety facilitating its over-expression or manipulation. Recent reviews highlight key milestones in the development of antibody libraries and their screening by phage display, and the impact of these technologies on drug discovery seems assured.
- Published
- 2009
- Full Text
- View/download PDF
32. Cocktails of human anti-cancer antibodies show a synergistic effect in nude mouse tumor xenografts.
- Author
-
Glassy MC, McKnight ME, Kotlan B, Glassy EF, and Koda K
- Subjects
- Animals, Cell Line, Tumor, Female, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Neoplasms, Experimental immunology, Transplantation, Heterologous, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Neoplasms, Experimental therapy
- Abstract
A panel of four natural human monoclonal IgG antibodies derived from B lymphocytes isolated from regional draining lymph nodes of cancer patients has been developed and characterized. The four human antibodies are termed, RM1, RM2, RM3, and RM4. The immunoreactivity of this panel of four human antibodies is restricted to tumor cells. Individually, these human MAbs show tumor targeting and are effective in inhibiting tumor growth in nude mouse xenograft models. When used in combination the antibodies show an additive effect in slowing down the progression of tumors in xenograft models suggesting that cocktails of antibodies may be useful in the clinic.
- Published
- 2007
33. Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin.
- Author
-
Kotlan B, Padanyi A, Batorfi J, Fulop V, Szigetvari I, Rajczy K, Penzes M, Gyodi E, Reti M, and Petranyi G
- Subjects
- Adult, Autoantibodies, Autoimmunity, Case-Control Studies, Female, Humans, Immunity, Cellular, Isoantibodies, Killer Cells, Natural immunology, Pregnancy, T-Lymphocytes, Cytotoxic immunology, Abortion, Habitual immunology, Abortion, Habitual therapy, Immunoglobulins, Intravenous therapeutic use
- Abstract
Problem: Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy., Method of Study: A complex immunological panel assay was offered to patients with reproductive failure without any other known cause. We focused here on the cellular immunological parameters., Results: High cytotoxic T lymphocyte precursor frequency and cell-mediated cytotoxic activity and a rather high natural killer cell activity were found in alloimmune RSA patients. Thirty-two patients were investigated by immunological assays and in 78% of the women an alloimmune background could be defined. The efficacy of IVIG treatment was 96% in this group., Conclusions: The novel cellular immunological assays proved to be favourable for the indication of RSA patients and showed the usefulness of this selection process for effective immunotherapy.
- Published
- 2006
- Full Text
- View/download PDF
34. Novel ganglioside antigen identified by B cells in human medullary breast carcinomas: the proof of principle concerning the tumor-infiltrating B lymphocytes.
- Author
-
Kotlan B, Simsa P, Teillaud JL, Fridman WH, Toth J, McKnight M, and Glassy MC
- Subjects
- Animals, Antigens, Neoplasm metabolism, B-Lymphocyte Subsets pathology, Binding Sites, Antibody genetics, Breast Neoplasms chemistry, Breast Neoplasms pathology, COS Cells, Carcinoma, Ductal, Breast chemistry, Carcinoma, Ductal, Breast immunology, Carcinoma, Ductal, Breast pathology, Carcinoma, Medullary chemistry, Carcinoma, Medullary pathology, Cell Line, Cell Line, Tumor, Clone Cells, DNA Mutational Analysis, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Gene Rearrangement, B-Lymphocyte, Light Chain, Humans, Immunoglobulin Fab Fragments chemistry, Immunoglobulin Fab Fragments genetics, Immunoglobulin Joining Region genetics, Immunoglobulin Joining Region isolation & purification, Immunoglobulin Variable Region genetics, Immunoglobulin Variable Region isolation & purification, Immunoglobulin lambda-Chains genetics, Immunoglobulin lambda-Chains isolation & purification, Lymphocytes, Tumor-Infiltrating pathology, Neoplasm Invasiveness, Peptide Library, Sequence Analysis, DNA, Antigens, Neoplasm immunology, B-Lymphocyte Subsets immunology, Breast Neoplasms immunology, Carcinoma, Medullary immunology, Gangliosides chemistry, Gangliosides immunology, Lymphocytes, Tumor-Infiltrating immunology
- Abstract
The potential tumor-recognizing capacity of B cells infiltrating human breast carcinoma is an important aspect of breast cancer biology. As an experimental system, we used human medullary breast carcinoma because of its heavy B lymphocytic infiltration paralleled to a relatively better prognosis. Ig-rearranged V region V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda genes, amplified by RT-PCR of the infiltrating B cells, were cloned, sequenced, and subjected to a comparative DNA analysis. A combinatorial single-chain variable fragment Ab minilibrary was constructed out of randomly selected V(H) and Vkappa clones and tested for binding activity. Our data analysis revealed that some of the V(H)-J(H), Vkappa-Jkappa, and Vlambda-Jlambda region sequences were being assigned to clusters with oligoclonal predominance, while other characteristics of the Ab repertoire were defined also. A tumor-restricted binder clone could be selected out of the single-chain variable fragment kappa minilibrary tested against membrane fractions of primary breast tumor cells and tumor cell lines, the V(H) of which proved to be the overexpressed V(H)3-1 cluster. The specific binding was confirmed by FACS analysis with primary breast carcinoma cells and MDA-MB 231 cell line. ELISA and thin layer chromatography dot-blot experiments showed this target Ag to be a ganglioside D3 (GD3). Our results are a proof of principle about the capacity of B cells infiltrating breast carcinomas to reveal key cancer-related Ags, such as the GD3. GD3-specific Abs may influence tumor cell progression and could be used for further development of diagnostic and/or therapeutic purposes.
- Published
- 2005
- Full Text
- View/download PDF
35. Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.
- Author
-
Simsa P, Teillaud JL, Stott DI, Tóth J, and Kotlan B
- Subjects
- Brain Stem Neoplasms immunology, Brain Stem Neoplasms pathology, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Humans, Retrospective Studies, B-Lymphocytes immunology, Breast Neoplasms immunology, Carcinoma, Ductal, Breast immunology, Genes, Immunoglobulin, Immunoglobulin Variable Region genetics, Lymphocytes, Tumor-Infiltrating immunology, Neoplasm Invasiveness pathology
- Abstract
A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.
- Published
- 2005
- Full Text
- View/download PDF
36. Generation of scFv from a phage display mini-library derived from tumor-infiltrating B-cells.
- Author
-
Gruel N, Kotlan B, Beuzard M, and Teillaud JL
- Subjects
- B-Lymphocytes immunology, Neoplasms immunology, B-Lymphocytes metabolism, Immunoglobulin Variable Region genetics, Peptide Library, Reverse Transcriptase Polymerase Chain Reaction methods
- Published
- 2002
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.