Publication Date:
2019-11-13
Description:
Introduction: Autologous anti-BCMA CAR-T cells have been successfully used in clinical trials for the treatment of relapsed refractory Multiple Myeloma (rrMM), achieving high initial response rates (〉80%). However, in some patients these therapeutic responses were not sustained long-term and patients relapsed within 12-18 months1,2. Poor T cell fitness leading to early CAR-T cell exhaustion as well as BCMA negative tumour escape are thought to be factors contributing to treatment failure. In this study we describe for the first time the activity of an allogeneic anti-BCMA CAR-T cell product derived from young healthy donors (HD) against primary MM cells using patient bone marrow (BM) biopsies. In addition, we compare the performance of HD and MM patient-derived anti-BCMA CAR-T cells. Results: We have developed a clinically relevant model to test the efficacy of allogeneic anti-BCMA CAR-T cells against primary MM cells. This ex vivo platform uses bulk BM biopsies from MM patients to represent the heterogeneity seen in MM tumours in vivo, including their complex genomic background and unique immunosuppressive microenvironment. Newly diagnosed patients and rrMM patients with high risk genetics are included in the cohort. Using this model we show that allogeneic anti-BCMA CAR-T cells efficiently eliminate primary MM cells after 4 hours of co-culture, in a dose-dependent manner (n=9). These allogeneic anti-BCMA CAR-T cells specifically target BCMA-expressing primary MM cells (including samples with low BCMA levels and high risk genomic abnormalities, with specific anti-BCMA CAR-T cell killing of 13-73%), whilst not affecting non-tumour cells in the BM microenvironment. Moreover, we show that anti-BCMA CAR-T cells become significantly activated after exposure to CD138+ MM cells (〉50% CD25+ T cells versus
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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