Anti-CD37 targeted immunotherapy of B-Cell malignancies

Payandeh, Zahra; Noori, Effat; Khalesi, Bahman; Mard-Soltani, Maysam; Abdolalizadeh, Jalal; Khalili, Saeed

doi:10.1007/s10529-018-2612-6

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…However, many patients eventually relapse and become resistant to treatment, creating an unmet need for alternative therapeutic strategies. In recent years, the tetraspanin plasma membrane protein CD37 has gained renewed interest as a promising therapeutic target for B-cell malignancies [4][5][6][7] . CD37 is selectively expressed on mature B cells and has limited or no expression on other hematopoietic cells such as T cells and NK cells, granulocytes, monocytes and dendritic cells [8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

“…In cancer, CD37 is highly expressed on malignant B cells in a variety of B-cell lymphomas and leukemias, including NHL and CLL 14,15 . To date, multiple CD37targeting agents have shown preclinical or clinical efficacy [5][6][7] , including antibody drug conjugates 16,17 , a small modular immuno-pharmaceutical protein (SMIP) 18 , an antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) capacity 19 , a radiolabeled antibody 20 and chimeric antigen receptor (CAR) T cells 21 . The effector mechanisms of these agents include direct cytotoxicity mediated through conjugated cytotoxic or radioactive payloads, classical FcγR-mediated effector functions such as ADCC, and T-cell mediated cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…The effector mechanisms of these agents include direct cytotoxicity mediated through conjugated cytotoxic or radioactive payloads, classical FcγR-mediated effector functions such as ADCC, and T-cell mediated cytotoxicity. Interestingly, CD37 antibody-based therapeutics currently in (pre-)clinical development are poor inducers of complement-dependent cytotoxicity (CDC) [5][6][7] , another powerful Fc-mediated effector mechanism for killing hematological cancer cells 22,23 .…”

Section: Introductionmentioning

confidence: 99%

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DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies

et al. 2020

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Tetraspanin CD37 has recently received renewed interest as a therapeutic target for B-cell malignancies. Although complement-dependent cytotoxicity (CDC) is a powerful Fc-mediated effector function for killing hematological cancer cells, CD37-specific antibodies are generally poor inducers of CDC. To enhance CDC, the E430G mutation was introduced into humanized CD37 monoclonal IgG1 antibodies to drive more efficient IgG hexamer formation through intermolecular Fc-Fc interactions after cell surface antigen binding. DuoHexaBody-CD37, a bispecific CD37 antibody with the E430G hexamerization-enhancing mutation targeting two non-overlapping epitopes on CD37 (biparatopic), demonstrated potent and superior CDC activity compared to other CD37 antibody variants evaluated, in particular ex vivo in patient-derived chronic lymphocytic leukemia cells. The superior CDC potency was attributed to enhanced IgG hexamerization mediated by the E430G mutation in combination with dual epitope targeting. The mechanism of action of DuoHexaBody-CD37 was shown to be multifaceted, as it was additionally capable of inducing efficient antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis in vitro. Finally, potent antitumor activity in vivo was observed in cell line-and patient-derived xenograft models from different B-cell malignancy subtypes. These encouraging preclinical results suggest that DuoHexaBody-CD37 (GEN3009) may serve as a potential therapeutic antibody for the treatment of human B-cell malignancies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies

et al. 2020

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“…The expression of CD37 is detected in CLL, Burkitt lymphoma (BL), MCL, and FL, 119,120 and it is involved in various biological processes, such as cell adhesion, proliferation, differentiation, intercellular communication via exosomes and immune response. 121 Small modular immunopharmaceuticals (SMIPs) are disulfidelinked single-chain proteins comprised of one antigen-binding region (V H /V L ), a hinge, and an Fc domain of the human IgG1 region (CH2-CH3). Due to their smaller size, SMIPs may have better tissue penetration than mAbs.…”

Section: Cd37mentioning

confidence: 99%

Advances in targeted therapy for malignant lymphoma

Wang

Qin

Huo

et al. 2020

Sig Transduct Target Ther

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The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.Signal Transduction and Targeted Therapy (2020) 5:15; https://doi.

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“…Most carbohydrate antigens are T-cell-independent and produce a weak immune response (Payandeh et al 2018). Thus, while carbohydrate antigens are potentially suited for immune recognition and killing, their use in cancer vaccines has remained challenging due to the difficulties associated with overcoming immunotolerance and immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in carbohydrate-based cancer vaccines

et al. 2019

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Cancer is a complex multifactorial disease for which many promising therapeutic strategies such as immunotherapy are emerging. Malignant cells frequently express aberrant cell surface carbohydrates, which differentiate them from normal ''healthy'' cells. This characteristic presents a window for the development of synthetic carbohydrate antigen-based cancer vaccines which can be recognized by the immune system and can bring about T cell-dependent immune responses. Antibodies generated against the carbohydrate antigens partake in the inactivation of carbohydrate-decorated cancer cells, by slowing down tumor cell growth and inducing cancer cell apoptosis. Novel synthetic strategies for carbohydrate antigens have led to several synthetic cancer vaccine candidates. In the present review, we describe the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.

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Anti-CD37 targeted immunotherapy of B-Cell malignancies

Cited by 21 publications

References 33 publications

DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies

DuoHexaBody-CD37®, a novel biparatopic CD37 antibody with enhanced Fc-mediated hexamerization as a potential therapy for B-cell malignancies

Advances in targeted therapy for malignant lymphoma

Recent advances in carbohydrate-based cancer vaccines

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