Single cell Dissection of Resistance to anti-BCMA CAR-T cell Therapy

Ledergor, Guy; McCarthy, Elizabeth W.; Shah, Nina; Wong, Sandy W.; Chang, Hewitt; Fan, Si; Shao, Evans; Gray, Lissa; Cheung, Alexander; Kwek, Serena S.; Bylsma, Sophia; Favero, Samuel Del; Wustrack, Rosanna; Spitzer, Matthew H.; Wolf, Jeffrey L.; Martin, Thomas; Ye, Chun Jimmie; Fong, Lawrence

doi:10.1016/j.clml.2019.09.038

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“…BCMA-targeted CAR cells induce deep response in RRMM, and could eliminate bulky extramedullary lesions, but the responses are often temporary. The main reasons for the relapse are the down-regulation or loss of BCMA expression on the MM cell surface and CAR T-cell exhaustion, which could be the result of CAR T-cell induced trogocytosis or the suppressive myeloid cells in the myeloma niche [58][59][60]. Dual-antigen targeting CAR T-cell strategies reduce the risk of BCMA escape and increase the targeting antigen of MM cells.…”

Section: Resultsmentioning

confidence: 99%

Immunotherapeutic strategies targeting B cell maturation antigen in multiple myeloma

Fang

Hou

2021

Military Med Res

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Multiple myeloma (MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen (BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease (MRD) negative patients, will also be discussed.

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Section: Resultsmentioning

confidence: 99%