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13 results on '"Dawson, Margaret J."'

1. Supplementary Figure 1 from Reprogramming CD19-Specific T Cells with IL-21 Signaling Can Improve Adoptive Immunotherapy of B-Lineage Malignancies

Author

Singh, Harjeet, primary, Figliola, Matthew J., primary, Dawson, Margaret J., primary, Huls, Helen, primary, Olivares, Simon, primary, Switzer, Kirsten, primary, Mi, Tiejuan, primary, Maiti, Sourindra, primary, Kebriaei, Partow, primary, Lee, Dean A., primary, Champlin, Richard E., primary, and Cooper, Laurence J.N., primary

Published
2023
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2. Data from Reprogramming CD19-Specific T Cells with IL-21 Signaling Can Improve Adoptive Immunotherapy of B-Lineage Malignancies

Author

Singh, Harjeet, primary, Figliola, Matthew J., primary, Dawson, Margaret J., primary, Huls, Helen, primary, Olivares, Simon, primary, Switzer, Kirsten, primary, Mi, Tiejuan, primary, Maiti, Sourindra, primary, Kebriaei, Partow, primary, Lee, Dean A., primary, Champlin, Richard E., primary, and Cooper, Laurence J.N., primary

Published
2023
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3. Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells

Author

Kebriaei, Partow, primary, Singh, Harjeet, additional, Huls, M. Helen, additional, Figliola, Matthew J., additional, Bassett, Roland, additional, Olivares, Simon, additional, Jena, Bipulendu, additional, Dawson, Margaret J., additional, Kumaresan, Pappanaicken R., additional, Su, Shihuang, additional, Maiti, Sourindra, additional, Dai, Jianliang, additional, Moriarity, Branden, additional, Forget, Marie-Andrée, additional, Senyukov, Vladimir, additional, Orozco, Aaron, additional, Liu, Tingting, additional, McCarty, Jessica, additional, Jackson, Rineka N., additional, Moyes, Judy S., additional, Rondon, Gabriela, additional, Qazilbash, Muzaffar, additional, Ciurea, Stefan, additional, Alousi, Amin, additional, Nieto, Yago, additional, Rezvani, Katy, additional, Marin, David, additional, Popat, Uday, additional, Hosing, Chitra, additional, Shpall, Elizabeth J., additional, Kantarjian, Hagop, additional, Keating, Michael, additional, Wierda, William, additional, Do, Kim Anh, additional, Largaespada, David A., additional, Lee, Dean A., additional, Hackett, Perry B., additional, Champlin, Richard E., additional, and Cooper, Laurence J.N., additional

Published
2016
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4. Clinical Application of Sleeping Beauty and Artificial Antigen Presenting Cells to Genetically Modify T Cells from Peripheral and Umbilical Cord Blood

Author

Huls, M. Helen, Figliola, Matthew J., Dawson, Margaret J., Olivares, Simon, Kebriaei, Partow, Shpall, Elizabeth J., Champlin, Richard E., Singh, Harjeet, and Cooper, Laurence J.N.

Subjects
Lymphoma, T-Lymphocytes, Immunology, Adoptive, Biomedical Engineering, T cells, Receptors, Antigen, T-Cell, Antigen-Presenting Cells, Transposases, Lymphoid, Biochemistry, Genetics, Sleeping Beauty, Humans, Issue 72, Antigens, Molecular Biology, Cancer Biology, Cryopreservation, Antigen Presentation, Leukemia, CD19, Umbilical Cord Blood, DNA, Superhelical, Hematology, Gene Therapy, Peripheral Blood, Fetal Blood, Clinical Trial, Cellular Biology, Electroporation, Medicine, Immunotherapy, Genetic Engineering, K562 Cells, Chimeric Antigen Receptor, Artificial Antigen Presenting Cells, Plasmids
Abstract

The potency of clinical-grade T cells can be improved by combining gene therapy with immunotherapy to engineer a biologic product with the potential for superior (i) recognition of tumor-associated antigens (TAAs), (ii) persistence after infusion, (iii) potential for migration to tumor sites, and (iv) ability to recycle effector functions within the tumor microenvironment. Most approaches to genetic manipulation of T cells engineered for human application have used retrovirus and lentivirus for the stable expression of CAR(1-3). This approach, although compliant with current good manufacturing practice (GMP), can be expensive as it relies on the manufacture and release of clinical-grade recombinant virus from a limited number of production facilities. The electro-transfer of nonviral plasmids is an appealing alternative to transduction since DNA species can be produced to clinical grade at approximately 1/10(th) the cost of recombinant GMP-grade virus. To improve the efficiency of integration we adapted Sleeping Beauty (SB) transposon and transposase for human application(4-8). Our SB system uses two DNA plasmids that consist of a transposon coding for a gene of interest (e.g. 2(nd) generation CD19-specific CAR transgene, designated CD19RCD28) and a transposase (e.g. SB11) which inserts the transgene into TA dinucleotide repeats(9-11). To generate clinically-sufficient numbers of genetically modified T cells we use K562-derived artificial antigen presenting cells (aAPC) (clone #4) modified to express a TAA (e.g. CD19) as well as the T cell costimulatory molecules CD86, CD137L, a membrane-bound version of interleukin (IL)-15 (peptide fused to modified IgG4 Fc region) and CD64 (Fc-γ receptor 1) for the loading of monoclonal antibodies (mAb)(12). In this report, we demonstrate the procedures that can be undertaken in compliance with cGMP to generate CD19-specific CAR(+) T cells suitable for human application. This was achieved by the synchronous electro-transfer of two DNA plasmids, a SB transposon (CD19RCD28) and a SB transposase (SB11) followed by retrieval of stable integrants by the every-7-day additions (stimulation cycle) of γ-irradiated aAPC (clone #4) in the presence of soluble recombinant human IL-2 and IL-21(13). Typically 4 cycles (28 days of continuous culture) are undertaken to generate clinically-appealing numbers of T cells that stably express the CAR. This methodology to manufacturing clinical-grade CD19-specific T cells can be applied to T cells derived from peripheral blood (PB) or umbilical cord blood (UCB). Furthermore, this approach can be harnessed to generate T cells to diverse tumor types by pairing the specificity of the introduced CAR with expression of the TAA, recognized by the CAR, on the aAPC.

Published
2013

5. Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells

Author

Singh, Harjeet, primary, Figliola, Matthew J., additional, Dawson, Margaret J., additional, Olivares, Simon, additional, Zhang, Ling, additional, Yang, Ge, additional, Maiti, Sourindra, additional, Manuri, Pallavi, additional, Senyukov, Vladimir, additional, Jena, Bipulendu, additional, Kebriaei, Partow, additional, Champlin, Richard E., additional, Huls, Helen, additional, and Cooper, Laurence J. N., additional

Published
2013
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6. Reprogramming CD19-Specific T Cells with IL-21 Signaling Can Improve Adoptive Immunotherapy of B-Lineage Malignancies

Author

Singh, Harjeet, primary, Figliola, Matthew J., additional, Dawson, Margaret J., additional, Huls, Helen, additional, Olivares, Simon, additional, Switzer, Kirsten, additional, Mi, Tiejuan, additional, Maiti, Sourindra, additional, Kebriaei, Partow, additional, Lee, Dean A., additional, Champlin, Richard E., additional, and Cooper, Laurence J.N., additional

Published
2011
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7. piggyBac Transposon/Transposase System to Generate CD19-Specific T Cells for the Treatment of B-Lineage Malignancies

Author

Manuri, Pallavi V. Raja, primary, Wilson, Matthew H., additional, Maiti, Sourindra N., additional, Mi, Tiejuan, additional, Singh, Harjeet, additional, Olivares, Simon, additional, Dawson, Margaret J., additional, Huls, Helen, additional, Lee, Dean A., additional, Rao, Pulivarthi H., additional, Kaminski, Joseph M., additional, Nakazawa, Yozo, additional, Gottschalk, Stephen, additional, Kebriaei, Partow, additional, Shpall, Elizabeth J., additional, Champlin, Richard E., additional, and Cooper, Laurence J.N., additional

Published
2010
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8. Third Generation Chimeric Antigen Receptors Containing CD137 or CD134 Signaling Endodomains Augment CD19-Specific T-Cell Effector Function.

Author

Singh, Harjeet, primary, Gibbons, Hillary N, additional, Olivares, Simon, additional, Figliola, Matthew J., additional, Dawson, Margaret J., additional, Huls, Mary Helen, additional, Lee, Dean A, additional, Kebriaei, Partow, additional, Champlin, Richard E, additional, and Cooper, Laurence J.N., additional

Published
2009
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11. CD19-Specific T Cells for Treatment of Pediatric Acute Lymphocytic Leukemia Using Sleeping Beauty Transposition.

Author

Singh, Harjeet, primary, Manuri, Pallavi R., additional, Olivares, Simon, additional, Dara, Navid, additional, Dawson, Margaret J., additional, Huls, Helen, additional, Lee, Dean A., additional, Hackett, Perry B., additional, Kohn, Donald B., additional, Kebriaei, Partow, additional, Shpall, Elizabeth J., additional, Champlin, Richard, additional, and Cooper, Laurence, additional

Published
2007
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12. Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells

Author

Singh, Harjeet, Figliola, Matthew J., Dawson, Margaret J., Olivares, Simon, Zhang, Ling, Yang, Ge, Maiti, Sourindra, Manuri, Pallavi, Senyukov, Vladimir, Jena, Bipulendu, Kebriaei, Partow, Champlin, Richard E., Huls, Helen, and Cooper, Laurence J. N.

Subjects
T cells, CHIMERIC proteins, ANTIGEN receptors, CLINICAL trials, CD3 antigen, INTERLEUKIN-2, IMMUNOLOGY
Abstract

Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) is being evaluated in multiple clinical trials. Our current approach to adoptive immunotherapy is based on a second generation CAR (designated CD19RCD28) that signals through a CD28 and CD3-ζ endodomain. T cells are electroporated with DNA plasmids from the Sleeping Beauty (SB) transposon/transposase system to express this CAR. Stable integrants of genetically modified T cells can then be retrieved when co-cultured with designer artificial antigen presenting cells (aAPC) in the presence of interleukin (IL)-2 and 21. Here, we reveal how the platform technologies of SB-mediated transposition and CAR-dependent propagation on aAPC were adapted for human application. Indeed, we have initiated clinical trials in patients with high-risk B-lineage malignancies undergoing autologous and allogeneic hematopoietic stem-cell transplantation (HSCT). We describe the process to manufacture clinical grade CD19-specific T cells derived from healthy donors. Three validation runs were completed in compliance with current good manufacturing practice for Phase I/II trials demonstrating that by 28 days of co-culture on γ-irradiated aAPC ∼1010 T cells were produced of which >95% expressed CAR. These genetically modified and propagated T cells met all quality control testing and release criteria in support of infusion. [ABSTRACT FROM AUTHOR]

Published
2013
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13. T Cells Demonstrate Enhanced Specificity for CD19+Malignancies When Stimulated with IL-21.

Author

Singh, Harjeet, Huls, Mary Helen, Dawson, Margaret J., Mi, Tiejuan, Dotti, Gianpietro, Lee, Dean A., Kebriaei, Partow, Shpall, Elizabeth J., Hackett, Perry B., June, Carl H., Champlin, Richard E., and Cooper, Laurence J.N.

Abstract

T cells genetically modified to express CD19-specific chimeric antigen receptors (CARs) are being evaluated in early-phase clinical trials in patients with B-lineage malignancies. Therapeutic success is predicted by ability of infused CAR+T cells to both persist and kill in an antigen-dependent fashion. The first of these dual goals can be achieved by altering the CAR molecule to provide T-cell survival signals through a chimeric CD28 endodomain (designated CD19RCD28). We now report that altering the culturing microenvironment with IL-21 improves antigen-dependent cytolysis of T cells when propagated on CD19+artificial antigen presenting cells (aAPC) derived from K562. To test whether IL-21 acts in conjunction with CD28 signaling to support acquisition of redirected effector functions we electro-transferred quiescent T cells from peripheral blood with Sleeping Beautysystem DNA plasmids to introduce CD19RCD28 CAR transposon. Selective outgrowth of CAR+T cells was achieved on CD19+aAPC that provide co-stimulation with the addition of exogenous IL-2 and/or IL-21. When IL-21 was present there was preferential numeric expansion of CD19-specific CD8+T cells which lysed and produced IFN-g in response to CD19 (Figure). Furthermore, the CD8+CAR+T cells displayed a central memory (CM) cell surface phenotype characterized as CD62L+and CD28+. In contrast, genetically modified T cells propagated with exogenous IL-2 resulted in predominately CD19-specific CM CD4+T cells. Thus, cytokines can be used to tailor the CD8/CD4 ratio of CAR+T cells derived from peripheral blood. These data demonstrate that the dual goals of persistence and lysis can be achieved by altering CAR and the cytokine milieu and have implications for infusing CAR+T cells in next-generation immunotherapy trials.

Published
2008
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