BCMA-CAR-T cell(Takara Bio)

In recent years, chimeric antigen receptor (CAR)-engineered cellular therapy has brought remarkable advancements in cancer immunotherapy and autoimmune disease treatment. CAR T-cell therapy has demonstrated high efficacy in multiple myeloma (MM), but its durability is limited due to immune suppression within the tumor microenvironment (TME). This study elucidates how cancer-associated fibroblasts (CAFs) impair BCMA CAR T-cell function, and describes development of dual-specific CAR T-cells targeting CAFs. The results showed that CAFs promoted CAR T-cell exhaustion via TGF-β, PD-L1, IL-10, and the FAS/FASL pathway. BCMA-FAP and BCMA-CS1 CAR T cells exhibited enhanced cytotoxicity against MM cells and CAFs, overcoming TME-mediated suppression. E-cadherin-targeting CAR MSCs (Ecad CAR-MSCs) to address graft-versus-host disease (GvHD) were also developed for this study. These CAR MSCs significantly reduced GvHD by selectively accumulating in the intestinal epithelium, suppressing T-cell activation via IL-10 and galectin-9 while promoting Treg induction. These findings suggest that CAF-targeting dual-specific CAR T cells enhance the efficacy of MM immunotherapy, while Ecad CAR-MSCs offer a novel approach to treating GvHD. These approaches hold promise for clinical translation to improve outcomes in cellular therapy.

We attempt to analyze bone marrow findings and correlation with cytopenia(s) after anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell infusion in this study.

Relevant clinicopathologic data, including complete blood counts, neutrophil counts, relevant therapy history, and pre- and posttherapy bone marrow evaluations, were studied in 12 patients who received anti-BCMA CAR T-cell therapy.

Bone marrow findings after CAR T-cell therapy were available in 6 of 12 cases, 3 of which showed markedly hypocellular marrow with either markedly reduced or essentially absent hematopoiesis. One case showed a hypocellular marrow with trilineage hematopoiesis, while the remaining 2 cases showed persistent involvement by plasma cell myeloma. Reticulin stains did not reveal significant fibrosis. Ten patients had anemia, and 8 patients had leukopenia and thrombocytopenia at day 90 posttherapy. Long-term follow-up showed persistent disease in 10 of 12 cases.

Prolonged cytopenias occur in most patients after BCMA CAR T-cell therapy with bone marrow evaluations demonstrating associated marked hypocellularity with minimal or no hematopoiesis without an increase in fibrosis.