MB-103

Multiple myeloma is a plasma cell neoplasm. The emergence of proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has improved the prognosis of multiple myeloma patients. However, some patients are still insensitive to conventional therapy or frequently relapse after remission. Chemotherapy based on proteasome inhibitors or immunomodulatory drugs is ineffective in controlling the progression of relapsed refractory multiple myeloma. No consensus has been reached on treating relapsed refractory multiple myeloma to date. Recently chimeric antigen receptor T cells therapy has shown promising results that could achieve rapid remissions of patients and improve their prognoses. Additionally, most patients in chimeric antigen receptor T cell clinical trials were triple-refractory multiple myeloma patients, indicating that chimeric antigen receptor T cell immunotherapy could overcome drug resistance to new drugs. Since single immunotherapies are prone to acquired resistance, combination immunotherapies based on emerging immunotherapies may solve this issue. Achieving complete remission and minimal residual disease negative status as soon as possible is beneficial to patients. This paper reviewed the main chimeric antigen receptor T cell products in relapsed refractory multiple myeloma, and it explained the drug resistance mechanism and improvement methods of chimeric antigen receptor T cells therapy. This review summarized the best beneficiaries of chimeric antigen receptor T cell therapy and the salvage treatment of disease recurrence after chimeric antigen receptor T cell therapy, providing some ideas for the clinical application of chimeric antigen receptor T cells.

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)–specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied to tumors grown on the CAM. Four days post–CAR T cell treatment, HER2-expressing FaDu and SCC-47 tumors treated with CAR T showed reduced viable cancer cells as assessed by luciferase activity. This reduction in viable tumor cells was confirmed by histology, with lower Ki-67 staining observed in CAR T cell–treated tumors relative to T cell–treated controls. Persistence of CAR T in CAM and tumor tissue 4 days post-treatment was confirmed by CD3 staining. Altogether, our findings support further development of the chick CAM as an in vivo system for rapid, scalable screening of CAR T cell efficacy against human solid tumors.