A double-sided approach may help to prevent immune escape after engineered chimeric antigen receptor (CAR) T-cell therapy among patients with multiple myeloma, according to model-based research published in Blood Advances.

Although CAR-T therapy has improved survival periods among some patients with MM, relapse remains a problem. Early-stage research has suggested, however, that transgenic T cell receptor (eTCR-T cell) engineering may be an effective way to combat MM tumor heterogeneity.

This may be because eTCR-T cells are capable of safely targeting a wider set of antigens expressed by MM cells. For this model, researchers explored whether multi-antigen targeting using CAR- and TCR-engineered T-cells may be more effective at destroying MM cell lines than CAR-T therapy alone.

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The researchers initially evaluated BCMA and HLA expression in 3 bone marrow samples from patients with MM. Thereafter, the authors subjected the MM cell lines to overnight recognition by CAR-T cells, eTCR-T cells, or a combination thereof. Initial results suggested higher efficacy for inducing lysis in CAR T-cells than in eTCR-T cells, although a combination was similar to that seen with CAR T-cells alone.

A mouse model confirmed these finding, and suggested that eTCR-T cells would be unable to induce remission alone. When mice received double antigen-targeting therapy, however, MM cells were undetectable in bone marrow samples.

“Taken together, we developed a two-sided model for the outgrowth of immune escaped tumor cells after CAR-T cell or eTCR-T cell treatment.” the authors wrote in their report. “Single-antigen-targeting led to immune escape and outgrowth of tumor cells in vitro and in vivo, while dual-antigen-targeting completely cleared heterogeneous tumor cell populations.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.


Wachsmann TLA, Meeuwsen MH, Remst DFG, et al. Combining BCMA-targeting CAR-T with TCR-engineered T-cell therapy to prevent immune escape of multiple myeloma. Blood Adv. Published online August 11, 2023. doi:10.1182/bloodadvances.2023010410