Nat Commun: The absence of BCMA's double allegiant gene in patients with multiple myeloma causes the development of drug resistance in CAR-T therapy

Targeted BCMA (B-cell mature antigen) inlay antigen-subject (CAR) T-cell therapy has now shown far-reaching and long-lasting response effects in recurring refractic multiple myeloma (MM), the initial Phase I/II study showed that the therapy has an overall response rate of 73-100% and a full response rate of 31-69%.
, however, in previous studies, patients have been found to have a non-progressive survival of less than 12 months, and the recurrence of the disease and the production of obtained resistance may affect the effectiveness of the second CAR-T treatment.
response to CAR-T cell therapy and changes in the microenviron environment BCMA targeted chimic antigens (CAR) T cell therapy have shown a profound and lasting response in multiple myeloma.
, however, relapses after treatment are often observed and the mechanism of drug resistance remains unclear.
the intrinsic changes of tumors in the study, the researchers sequenced single-cell genomes from longitudinal samples from patients who relapsed after initial CAR-T cell therapy and did not respond to retreated treatment.
researchers screened sample information for a mutation in BCMA's double allethloym gene after the initial CAR-T treatment, one alleloloyding gene missing and the second alleloloyding gene carrying a mutation that causes the protein translation to terminate early.
researchers found that the absence of the gene's double alleloic gene led to a lack of CAR-T cell proliferation during the second treatment and a lack of soluble BCMA protein in the patient's serum.
, the results suggest that resistance from mutations in the BCMA gene should be noted in multiple myeloma cells that relapse after CAR-T treatment.