Comparison of CAR-T19 and autologous stem cell transplantation for refractory/relapsed non-Hodgkin’s lymphoma

Li, Caixia; Zhang, Ying; Zhang, Changfeng; Chen, Jia; Lou, Xiaoyan; Chen, Xiaochen; Kang, Liqing; Xu, Nan; Li, Minghao; Tan, Jingwen; Sun, Xiaoxiao; Zhou, Jin; Yang, Zhen; Zong, Xiangping; Wang, Pu; Xu, Tao; Qu, Changju; Huang, Haiwen; Jin, Zhengming; Yu, Lei; Wu, Depei

doi:10.1172/jci.insight.130195

Cited by 20 publications

(18 citation statements)

References 43 publications

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“…Whether CAR-T therapy has a role ahead of autoHCT remains an important clinical question. So far, a single-institution, nonrandomized, prospective study in patients with R/R NHL with an investigational CD19 CAR-T product has shown higher CR rates and superior overall survival, especially in patients with international prognostic index 3, with CD19 CAR-T compared with autologous stem cell transplant [93]. Ongoing randomized controlled trials are actively accruing for comparing CAR-T therapy (ie, axicabtagene ciloleucel [ZUMA-7, NCT03391466], tisagenlecleucel [BELINDA,NCT03570892], and lisocabtagene maraleucel [TRANSFORM, NCT03575351]) versus autoHCT in first R/R setting.…”

Section: What Are the New Advances For Car-t In Lymphoma?mentioning

confidence: 99%

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Jain

Bar

Kansagra

et al. 2019

Biology of Blood and Marrow Transplantation

150

121

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Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYM-RIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short-and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.

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Section: What Are the New Advances For Car-t In Lymphoma?mentioning

confidence: 99%

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Jain

Bar

Kansagra

et al. 2019

Biology of Blood and Marrow Transplantation

150

121

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“… 112 152 There is ongoing debate in the field of lymphoma treatment as to the potential for CAR T cell therapy to be used in conjunction with, or to replace, traditional autoSCT. 153 154 …”

Section: Integration Of Hematopoietic Stem Cell Transplant and Immunomentioning

confidence: 99%

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma

Neelapu

Adkins

Ansell

et al. 2020

J Immunother Cancer

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The recent development and clinical implementation of novel immunotherapies for the treatment of Hodgkin and non-Hodgkin lymphoma have improved patient outcomes across subgroups. The rapid introduction of immunotherapeutic agents into the clinic, however, has presented significant questions regarding optimal treatment scheduling around existing chemotherapy/radiation options, as well as a need for improved understanding of how to properly manage patients and recognize toxicities. To address these challenges, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts in lymphoma to develop a clinical practice guideline for the education of healthcare professionals on various aspects of immunotherapeutic treatment. The panel discussed subjects including treatment scheduling, immune-related adverse events (irAEs), and the integration of immunotherapy and stem cell transplant to form recommendations to guide healthcare professionals treating patients with lymphoma.

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“…CD3 + T cells were cultured and activated in vitro using anti-CD3/CD28 monoclonal antibodies (Miltenyi Biotec) in a 5% CO 2 atmosphere at 37°C for 18-24 h. The activated T cells were then transduced with lentivirus (CD19-CAR, BCMA-CAR and tandem CAR) for 48 h. We also tansduced the BCMA CAR (D1) followed by CD19-CAR (D2) to obtain the T cells expressed two scFv by transduced two lentivirus. After transduction, the CAR T cells were cultured and expanded in a 5% CO 2 atmosphere at 37°C for 14 days in AIM-V medium (Gibco, Grand Island, NY, USA), supplemented with 100 IU/mL recombinant human interleukin-2 (IL-2; Peprotech, Rocky Hill, NJ, USA), 5 ng/ml recombinant human IL-7 (Peprotech), 5 ng/mL recombinant human IL-15 (Peprotech) and 10% autologous plasma [19].…”

Section: Preparation Of Car T Cellsmentioning

confidence: 99%

Characterization of novel dual tandem CD19/BCMA chimeric antigen receptor T cells to potentially treat multiple myeloma

Kang

Zhang

et al. 2020

Biomark Res

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Background: Treatment with chimeric antigen receptor (CAR)-engineered T cells directed against the B-cell maturation antigen (BCMA) promoted transient recovery from multiple myeloma (MM). However, the absence of this antigen on immature plasma cells may limit the efficacy of this modality and facilitate relapse. The purpose of this study is to characterize a novel CAR that includes both a single-chain variable fragment (scFv)-BCMA and an scFv-CD19 in tandem orientation (tan-CAR) in an attempt to target both BCMA and CD19 expression on MM cells. Method: The scFv sequences from the anti-CD19 antibody FMC63 and the anti-BCMA antibody C11D5.3 were ligated in tandem with transmembrane and T-cell signaling domains to generate the tan-CAR construct. Specificity and efficacy of activated tan-CAR T cells were analyzed using in vitro proliferation, cytokine release, and cytolysis assays. We also evaluated the in vivo efficacy with a xenograft mouse model that included target tumor cells that expressed CD19 or BCMA and compared the results to those obtained with conventional CAR T cells. Results: The in vitro studies revealed specific activation of tan-CAR T cells by K562 cells that overexpressed CD19 and/or BCMA. Cell proliferation, cytokine release, and cytolytic activity were all comparable to the responses of single scFv CAR T cells. Importantly, in vivo studies of tan-CAR T cells revealed specific inhibition of tumor growth in the mouse xenograft model that included cells expressing both CD19 and BCMA. Systemic administration of tan-CAR T cells resulted in complete tumor remission, in contrast to the reduced efficacies of BCMA-CAR T and CD19-CAR T alone in this setting. Conclusion: We report the successful design and execution of novel tan-CAR T cells that promote significant antitumor efficacy against both CD19 and BCMA antigen-positive tumor cells in vitro and in vivo. The data from this study reveal a novel strategy that may help to reduce the rate of relapse in the treatment with single scFv-CAR T cells.

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Comparison of CAR-T19 and autologous stem cell transplantation for refractory/relapsed non-Hodgkin’s lymphoma

Abstract: Role of funding source: UniCar Therapy provided financial support for this clinical trial, including product manufacturing.

Cited by 20 publications

References 43 publications

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma

Characterization of novel dual tandem CD19/BCMA chimeric antigen receptor T cells to potentially treat multiple myeloma

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