6 results on '"Lootens N"'
Search Results
2. Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum.
- Author
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Ingels J, De Cock L, Stevens D, Mayer RL, Théry F, Sanchez GS, Vermijlen D, Weening K, De Smet S, Lootens N, Brusseel M, Verstraete T, Buyle J, Van Houtte E, Devreker P, Heyns K, De Munter S, Van Lint S, Goetgeluk G, Bonte S, Billiet L, Pille M, Jansen H, Pascal E, Deseins L, Vantomme L, Verdonckt M, Roelandt R, Eekhout T, Vandamme N, Leclercq G, Taghon T, Kerre T, Vanommeslaeghe F, Dhondt A, Ferdinande L, Van Dorpe J, Desender L, De Ryck F, Vermassen F, Surmont V, Impens F, Menten B, Vermaelen K, and Vandekerckhove B
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Dendritic Cells immunology, Lung Neoplasms immunology, Lung Neoplasms pathology, Cancer Vaccines immunology, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung therapy, Antigens, Neoplasm immunology, Cell Differentiation immunology, Vaccination, T-Lymphocytes immunology
- Abstract
Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
3. Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials.
- Author
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Ingels J, De Cock L, Mayer RL, Devreker P, Weening K, Heyns K, Lootens N, De Smet S, Brusseel M, De Munter S, Pille M, Billiet L, Goetgeluk G, Bonte S, Jansen H, Lint SV, Leclercq G, Taghon T, Menten B, Vermaelen K, Impens F, and Vandekerckhove B
- Subjects
- Antigens, Neoplasm genetics, Humans, Immunotherapy, Peptides, RNA, Messenger genetics, Cancer Vaccines, Lung Neoplasms, Neoplasms genetics, Neoplasms therapy
- Abstract
Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for cancer vaccines targeting mutated peptides expressed in a tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, and inclusion of these antigens in a vaccine requires the production of individual batches of patient-tailored mRNA. The authors have developed MIDRIX
NEO , a personalized mRNA-loaded dendritic cell vaccine targeting tumor neoantigens, which is currently being evaluated in a phase 1 clinical study in lung cancer patients. To facilitate this study, the authors set up a Good Manufacturing Practice (GMP)-compliant production process for the manufacture of small batches of personalized neoantigen-encoding mRNA. In this article, the authors describe the complete mRNA production process and the extensive quality assessment to which the mRNA is subjected. Validation runs have shown that the process delivers mRNA of reproducible, high quality. This process is now successfully applied for the production of neoantigen-encoding mRNA for the clinical evaluation of MIDRIXNEO . To the authors' knowledge, this is the first time that a GMP-based production process of patient-tailored neoantigen mRNA has been described., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
4. Treatment of a patient with severe cytomegalovirus (CMV) infection after haploidentical stem cell transplantation with donor derived CMV specific T cells.
- Author
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Ingels J, De Smet S, Heyns K, Lootens N, Segaert J, Taghon T, Leclercq G, Vermaelen K, Willems E, Baudoux E, Kerre T, Baron F, and Vandekerckhove B
- Subjects
- Cytomegalovirus, Humans, T-Lymphocytes, Tissue Donors, Cytomegalovirus Infections, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Objectives: Cytomegalovirus (CMV) infection is one of the most common complications in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. The classic antiviral treatments have shown clinical efficacy but are often associated with drug resistance. Reconstitution of CMV-specific cellular immunity is essential in controlling CMV infection; therefore, adoptive transfer of CMV-specific T cells is a promising treatment option. We treated a patient with a multidrug resistant CMV infection after haploidentical HSCT with CMV-specific T cells. Methods: The T cells were derived from the HSCT donor who was CMV seropositive. We generated the T cells by a short-term Good Manufacturing Practice (GMP) grade protocol in which a leukapheresis product of the HSCT donor was stimulated with the immunodominant antigen pp65 and interferon-γ secreting cells were isolated. A total of 5 × 10
5 T cells were administered to the patient within 30 hours after leukapheresis. Results: The patient was closely monitored for reconstitution of antiviral T cell immunity and viral replication after adoptive T cell transfer. We observed an in vivo expansion of both CD4+ and CD8+ CMV-specific T cells associated with a significant decrease in viral burden and clinical improvement. Conclusion: This case report further supports the feasibility and effectiveness of adoptive donor T cell transfer for the treatment of drug resistant CMV infections after allo-HSCT.- Published
- 2021
- Full Text
- View/download PDF
5. Selecting cord blood units for storage by CD34+ cell counts.
- Author
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Van Haute I, Lootens N, De Buck K, Verdegen L, Vander Steene V, Desmet S, Craeye D, and Vandekerckhove B
- Subjects
- Cell Separation methods, Humans, Antigens, CD34 metabolism, Blood Banking methods, Fetal Blood cytology, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells metabolism
- Published
- 2005
- Full Text
- View/download PDF
6. Viable CD34+ stem cell content of a cord blood graft: which measurement performed before transplantation is most representative?
- Author
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Van haute I, Lootens N, De Smet S, De Buck C, Verdegem L, Vanheusden K, Pinxteren J, and Vandekerckhove B
- Subjects
- Blood Cell Count methods, Cell Survival, Cryopreservation, Flow Cytometry, Humans, Leukocyte Count, Predictive Value of Tests, Reproducibility of Results, Transplantation, Homologous, Antigens, CD34 analysis, Blood Cell Count standards, Cord Blood Stem Cell Transplantation standards, Fetal Blood cytology
- Abstract
Background: Patient survival in allogeneic cord blood transplantation is critically dependent on total nucleated cell (TNC) count or total CD34+ cell count per kg of body weight. Theoretically, viable CD34+ cell measurement at the time of infusion should give a better indication of the suitability of a certain transplant. The relation between measurements on different samples and viable CD34+ cell count on the graft itself was analyzed., Study Design and Methods: Viable CD34+ cells were measured with a no-wash, single-platform technique with 7-aminoactinomycin D. Analysis was performed before freezing on the cord blood, after freezing and thawing on the cord blood unit itself, and on various samples., Results: Cord blood volume correlated poorly with viable CD34+ cell content (r=0.24) as did initial TNC count and WBC count (r=0.57 and r=0.48, respectively). In contrast, viable CD34 cell content determined before freezing correlated well with viable CD34 cell content of the graft (r=0.91) but was on average 25 percent higher than after freezing and thawing. The best correlations with the CD34+ cell content of the cord blood unit were obtained with CD34 cell measurements on a separate cryovial (r=0.95). These CD34 cell measurements on frozen samples were found to be very reproducible (r=0.96)., Conclusion: Viable CD34 cell count of the graft is both accurate and precise when measured on a separate sample frozen together with the cord blood unit. This measurement can be performed by the transplant center to exclude between-laboratory variability.
- Published
- 2004
- Full Text
- View/download PDF
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