Updates on CAR T‐cell therapy in B‐cell malignancies

Jacoby, Elad; Shahani, Shilpa; Shah, Nirali N.

doi:10.1111/imr.12774

Cited by 66 publications

(41 citation statements)

References 173 publications

(361 reference statements)

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“…Immunotherapy is thought to be a promising treatment of tumors including MM [16,17] . Exploring a suitable tumor-speci c antigen, which is expressed in tumors but not in other normal tissues, or tumorassociated antigen, which is overexpressed in tumors but poorly expressed in normal cells, is crucial in active immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

A novel human multiple myeloma cell line with genetic abnormality of 1q21 gains only and CKS1B overexpression

Yi¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background Multiple myeloma (MM) remains an incurable hematologic malignancy mainly due to its cytogenetic abnormalities. It is important to establish permanent malignant MM cell lines as effective tools to develop more effective therapies. Results We established and characterized a new multiple myeloma (MM) cell line CZ2 from the pleural effusion of a 70-year-old man. Using nephelometry and flow cytometry, cells with typical plasma cell morphology but not classical plasma cell phenotype were found to be non-immunoglobulin-secretary cells. FISH analysis of cells revealed a unique characteristic that there is only gain of 1q21 region(1q21+), while no other common cytogenetic abnormalities of multiple myeloma such as deletion of 17p(17p-), deletion of 13q(13q-) and translocation of IgH. In addition, the original cell line maintains its single cytogenetic abnormality. Meanwhile, CKS1B, an adverse prognostic gene which is located in 1q21 region was highly expressed in CZ2 using western blotting. Knockdown of CKS1B could reduce cell viability in addition that cleaved PARP and cleaved caspase3 would be decreased. Conclusions Therefore, CZ2 provides a suitable material for cellular and molecular studies of multiple myeloma with only 1q21 abnormality. The cell line characterized by gain of 1q21 and high expression of CKS1B is an important model for studies of myeloma cell growth and drug resistance during therapy.

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Section: Discussionmentioning

confidence: 99%

A novel human multiple myeloma cell line with genetic abnormality of 1q21 gains only and CKS1B overexpression

Yi¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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“…This has fueled the development of dual antigen-targeted approaches to overcome antigen escape [66]. Several early-phase CAR-T-cell clinical trials investigating the combined targeting of CD19 and another antigen, such as CD22 and CD20, have now been initiated in patients with CD19 + B-cell malignancies [67,68]. Similarly, in MM, a dual antigen approach with BCMA and CD19 CAR-T cells has already been published [44], and novel MM antigens (e.g., GPRC5D) are being identified at rapid pace for rational combined targeting with BCMA [51,69].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data

Roex

Feys²,

Béguin

et al. 2020

Pharmaceutics

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Chimeric antigen receptor (CAR)-T-cell therapy is an innovative form of adoptive cell therapy that has revolutionized the treatment of certain hematological malignancies, including B-cell non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (ALL). The treatment is currently also being studied in other B-cell neoplasms, including multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). CD19 and B-cell maturation antigen (BCMA) have been the most popular target antigens for CAR-T-cell immunotherapy of these malignancies. This review will discuss the efficacy and toxicity data from the pivotal clinical studies of CD19- and BCMA-targeted CAR-T-cell therapies in relapsed/refractory B-cell malignancies (NHL, ALL, CLL) and MM, respectively.

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“…The ideal antigenic targets should be highly cancer-specific, be universally applicable to all patients and cancer types and enable treatment without the requirement for AHCT. This last decade has seen the rise of anti-CD19 chimeric antigen receptor (CAR)-modified T cells which fulfill some of these characteristics (86). Despite excellent clinical results in childhood acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and myeloma, current CAR-based approaches are limited to a subset of B-cell antigens [CD19, CD22 (87), B-cell maturation antigen-BCMA (88)].…”

Section: Tumor-associated Antigens (Taa)mentioning

confidence: 99%

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

et al. 2020

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Over the last decades, T-cell immunotherapy has revealed itself as a powerful, and often curative, strategy to treat blood cancers. In hematopoietic cell transplantation, most of the so-called graft-vs.-leukemia (GVL) effect hinges on the recognition of histocompatibility antigens that reflect immunologically relevant genetic variants between donors and recipients. Whether other variants acquired during the neoplastic transformation, or the aberrant expression of gene products can yield antigenic targets of similar relevance as the minor histocompatibility antigens is actively being pursued. Modern genomics and proteomics have enabled the high throughput identification of candidate antigens for immunotherapy in both autologous and allogeneic settings. As such, these major histocompatibility complex-associated tumor-specific (TSA) and tumor-associated antigens (TAA) can allow for the targeting of multiple blood neoplasms, which is a limitation for other immunotherapeutic approaches, such as chimeric antigen receptor (CAR)-modified T cells. We review the current strategies taken to translate these discoveries into T-cell therapies and propose how these could be introduced in clinical practice. Specifically, we discuss the criteria that are used to select the antigens with the greatest therapeutic value and we review the various T-cell manufacturing approaches in place to either expand antigen-specific T cells from the native repertoire or genetically engineer T cells with minor histocompatibility antigen or TSA/TAA-specific recombinant T-cell receptors. Finally, we elaborate on the current and future incorporation of these therapeutic T-cell products into the treatment of hematological malignancies.

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Updates on CAR T‐cell therapy in B‐cell malignancies

Cited by 66 publications

References 173 publications

A novel human multiple myeloma cell line with genetic abnormality of 1q21 gains only and CKS1B overexpression

A novel human multiple myeloma cell line with genetic abnormality of 1q21 gains only and CKS1B overexpression

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data

T-Cell Immunotherapies Targeting Histocompatibility and Tumor Antigens in Hematological Malignancies

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