Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Bétrian, Sarah; Ysebaert, Loïc; Heider, Karl-Heinz; Delord, J.P.; Fournié, Jean‐Jacques; Quillet‐Mary, Anne

doi:10.1038/bcj.2016.106

Cited by 13 publications

(10 citation statements)

References 14 publications

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“…These findings have potential practical implications, as a combination treatment with SMIP-016 and the PI3Kδ isoform-specific inhibitor idelalisib has demonstrated efficacy in preclinical in vitro studies [ 44 ]. Similar observations have been made in the case of another chimeric anti-CD37 antibody-BI 836826, which has demonstrated increased efficacy against CLL cells in vitro when combined with PI3K inhibitor idelalisib [ 50 ].…”

Section: Cd37 In B Cell Lymphoma and Leukemiasupporting

confidence: 73%

CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

Bobrowicz

Kubacz

Ślusarczyk

et al. 2020

IJMS

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CD37 is a tetraspanin expressed prominently on the surface of B cells. It is an attractive molecular target exploited in the immunotherapy of B cell-derived lymphomas and leukemia. Currently, several monoclonal antibodies targeting CD37 as well as chimeric antigen receptor-based immunotherapies are being developed and investigated in clinical trials. Given the unique role of CD37 in the biology of B cells, it seems that CD37 constitutes more than a docking point for monoclonal antibodies, and targeting this molecule may provide additional benefit to relapsed or refractory patients. In this review, we aimed to provide an extensive overview of the function of CD37 in B cell malignancies, providing a comprehensive view of recent therapeutic advances targeting CD37 and delineating future perspectives.

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Section: Cd37 In B Cell Lymphoma and Leukemiasupporting

confidence: 73%

CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

Bobrowicz

Kubacz

Ślusarczyk

et al. 2020

IJMS

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“…In particular, the monoclonal anti-CD37 antibody BI836826 and the humanized monospecific protein therapeutic otlertuzumab showed prolonged progression-free survival alone and in combination with other agents for the treatment of relapse/refractory CLL. 24,35,36 Similarly, IMGN529, an immunoconjugate used for the treatment of non-Hodgkin lymphoma, showed safety and preliminary evidence of activity in patients with DLBCL. 37,38 In a recent abstract presentation at the International Conference on Malignant Lymphoma in Lugano, Switzerland, the AGS67E antibody-drug conjugate directed to CD37 was found to be well tolerated in a phase 1 dose escalation trial, with neutropenia as the dose-limiting toxicity.…”

Section: Discussionmentioning

confidence: 99%

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Scarfò

Ormhøj

Frigault

et al. 2018

Blood

121

102

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Chimeric antigen receptor (CAR) T cells have emerged as a novel form of treatment of patients with B-cell malignancies. In particular, anti-CD19 CAR T-cell therapy has effected impressive clinical responses in B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma. However, not all patients respond, and relapse with antigen loss has been observed in all patient subsets. Here, we report on the design and optimization of a novel CAR directed to the surface antigen CD37, which is expressed in B-cell non-Hodgkin lymphomas, in chronic lymphocytic leukemia, and in some cases of cutaneous and peripheral T-cell lymphomas. We found that CAR-37 T cells demonstrated antigen-specific activation, cytokine production, and cytotoxic activity in models of B- and T-cell lymphomas in vitro and in vivo, including patient-derived xenografts. Taken together, these results are the first showing that T cells expressing anti-CD37 CAR have substantial activity against 2 different lymphoid lineages, without evidence of significant T-cell fratricide. Furthermore, anti-CD37 CARs were readily combined with anti-CD19 CARs to generate dual-specific CAR T cells capable of recognizing CD19 and CD37 alone or in combination. Our findings indicate that CD37-CAR T cells represent a novel therapeutic agent for the treatment of patients with CD37-expressing lymphoid malignancies.

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“…Although phase 1/2 studies are limited by small patient numbers and dose variations, response rates with BI 836826 compare favorably to otlertuzumab or rituximab as single agents in CLL [9,10], and are in the range observed with ofatumumab and obinutuzumab [6,11]. Moreover, there is preclinical rationale to use BI 836826 in combination with cytotoxics and nonchemotherapy agents such as idelalisib [12,13].…”

Section: To the Editormentioning

confidence: 99%

Phase 1 first-in-human trial of the anti-CD37 antibody BI 836826 in relapsed/refractory chronic lymphocytic leukemia

et al. 2019

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Idelalisib improves CD37 antibody BI 836826 cytotoxicity against chemo-resistant /relapse-initiating CLL cells: a rationale for combination treatment

Cited by 13 publications

References 14 publications

CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

CD37 in B Cell Derived Tumors—More than Just a Docking Point for Monoclonal Antibodies

Anti-CD37 chimeric antigen receptor T cells are active against B- and T-cell lymphomas

Phase 1 first-in-human trial of the anti-CD37 antibody BI 836826 in relapsed/refractory chronic lymphocytic leukemia

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