High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

Elfrink, Suraya; Winde, Charlotte M. de; Brand, Michiel van den; Berendsen, Madeleine R.; Roemer, Margaretha G.M.; Arnold, Frank; Janssen, Luuk; Schaaf, Alie van der; Jansen, Erik; Groenen, Patricia J.T.A.; Eijkelenboom, Astrid; Stevens, Wendy B C; Hess, Corine J.; Krieken, J. Han van; Vermaat, Joost S.P.; Cleven, Arjen H.G.; Groen, Ruben A.L. De; Neviani, Viviana; Jong, Daphne de; Deventer, Sjoerd van; Scheijen, Blanca; Spriel, Annemiek B. van

doi:10.1182/blood.2019001185

Cited by 19 publications

(16 citation statements)

References 24 publications

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“…Recently, in DLBCL patients, it has been demonstrated that mutations leading to defective glycosylation and trafficking of CD37 that, in consequence, lead to the lack of CD37 on the cell membrane are present only in the population with immune-privileged site-associated tumors. Therefore, it has been suggested that CD37 loss provides a survival advantage in the otherwise stimulus-poor environment [ 51 ].…”

Section: Cd37 In B Cell Lymphoma and Leukemiamentioning

confidence: 99%

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 Leukemiamentioning

confidence: 99%

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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“…Thus, CD37-CAR-T cells can improve the outcome of CD19-negative relapsed lymphoma patients. Bi-specific CD37-CD19 CAR-T cells can be important to increase the efficacy of CD19-CAR-T cells and also important in case of CD37 antigen loss due to missense mutations or other mechanisms [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma

Golubovskaya

Zhou

et al. 2021

Cancers

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CD19 and CD37 proteins are highly expressed in B-cell lymphoma and have been successfully targeted with different monotherapies, including chimeric antigen receptor (CAR)-T cell therapy. The goal of this study was to target lymphoma with novel CD37, humanized CD37, and bi-specific humanized CD37-CD19 CAR-T cells. A novel mouse monoclonal anti-human CD37 antibody (clone 2B8D12F2D4) was generated with high binding affinity for CD37 antigen (KD = 1.6 nM). The CD37 antibody specifically recognized cell surface CD37 protein in lymphoma cells and not in multiple myeloma or other types of cancer. The mouse and humanized CD37-CAR-T cells specifically killed Raji and CHO-CD37 cells and secreted IFN-gamma. In addition, we generated bi-specific humanized hCD37-CD19 CAR-T cells that specifically killed Raji cells, CHO-CD37, and Hela-CD19 cells and did not kill control CHO or Hela cells. Moreover, the hCD37-CD19 CAR-T cells secreted IFN-gamma against CD37-positive and CD19-positive target CHO-CD37, Hela-CD19 cells, respectively, but not against CD19 and CD37-negative parental cell line. The bi-specific hCD37-CD19 significantly inhibited Raji xenograft tumor growth and prolonged mouse survival in NOD scid gamma mouse (NSG) mouse model. This study demonstrates that novel humanized CD37 and humanized CD37-CD19 CAR-T cells specifically targeted either CD37 positive or CD37 and CD19-positive cells and provides a basis for future clinical studies.

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“…In case of CD37, because of its restricted expression and strong biological role in mature B lymphocytes, it has been clinically targeted with monoclonal antibody for leukemia treatment. The efficacy of this approach, however, appears challenged by emerging incidence of mutations at the critical domain or deletion of this gene in biopsies in some patient populations [ 16 ].…”

Section: Clinical Significance Of Deregulation Of Cd151 and Its Associated Networkmentioning

confidence: 99%

“…Despite their high structural similarity, tetraspanins seem to differ both in their functions and signal transduction. Notably, a single point mutation or deletion of the CD151 or CD37 gene leads to kidney and skin malfunctions or defective immunity in both humans and mice, while the targeted deletion or alternative splicing of tetraspanin CD9, CD37, CD53, CD81, and CD82 (singularly or in combination) profoundly impairs function or maturation of B and T lymphocytes and myeloid lineage cells or tissue metabolism in vertebrates [ 4 , 7 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Aberrant expression of tetraspanins have been observed in tumor tissues across a wide spectrum of cancer types, ranging from breast, colon, ovarian and prostate cancers to glioblastoma and leukemia [ 1 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

Erfani

Hua

Pan

et al. 2021

Cancers

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As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and the Wnt/β-catenin pathway, as well as the dynamics of exosome and cellular metabolism. Finally, we discuss the implications of the highly plastic nature and epigenetic susceptibility of CD151 expression, function, and signaling for clinical diagnosis and therapeutic intervention for human cancer.

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High frequency of inactivating tetraspanin CD37 mutations in diffuse large B-cell lymphoma at immune-privileged sites

Abstract: Key Points Loss-of-function mutations in CD37 occur predominantly in diffuse large B-cell lymphoma at immune-privileged sites. CD37-mutated lymphoma B cells show impaired CD37 cell-surface localization, which may have implications for anti-CD37 therapies.

Cited by 19 publications

References 24 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

Novel CD37, Humanized CD37 and Bi-Specific Humanized CD37-CD19 CAR-T Cells Specifically Target Lymphoma

The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

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