Dual Targeting with CAR T Cells to Limit Antigen Escape in Multiple Myeloma

Area of Science:

• Immunotherapy
• Oncology
• Cellular Therapy

Background:

• Adoptive T-cell therapy shows promise for hematologic cancers but is limited by tumor antigen escape.
• Relapses frequently occur when cancer cells lose expression of the targeted antigen.
• Targeting multiple antigens simultaneously is a crucial strategy to overcome therapeutic resistance.

Purpose of the Study:

• To investigate the efficacy of dual-targeting chimeric antigen receptor (CAR) T cells in preclinical multiple myeloma models.
• To evaluate the potential of simultaneously targeting B-cell maturation antigen (BCMA) and G protein-coupled receptor, class C, group 5, member D (GPRC5D) to prevent tumor escape.

Main Methods:

• Development of T cells engineered with chimeric antigen receptors specific for both BCMA and GPRC5D.
• Preclinical testing in multiple myeloma models to assess anti-tumor activity and resistance to antigen escape.

Main Results:

• Simultaneous targeting of BCMA and GPRC5D with engineered T cells demonstrated potent anti-myeloma activity in preclinical models.
• This dual-targeting strategy effectively prevented the outgrowth of tumor cells lacking expression of a single antigen.

Conclusions:

• Simultaneous targeting of BCMA and GPRC5D represents a promising strategy to overcome antigen escape in multiple myeloma.
• Dual-targeted CAR T-cell therapy may offer a more durable and effective treatment option for patients with hematologic malignancies.