Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Multiple myeloma is an incurable plasma cell malignancy.
• Advances in treatment have improved outcomes but not a cure.

Purpose of the Study:

• Develop novel chimeric antigen receptors (CAR) for multiple myeloma treatment.
• Investigate combinatorial therapy using CAR T cells and lenalidomide for enhanced efficacy.

Main Methods:

• Redirected central memory T cells to express CS1-specific CARs.
• Adoptively transferred CS1 CAR T cells into multiple myeloma tumor-bearing mice.
• Expanded CS1 CAR T cells with lenalidomide in vitro and compared phenotypes and functions.
• Administered combinatorial therapy of CS1 CAR T cells and lenalidomide to mice.

Main Results:

• CS1 CAR T cells demonstrated efficient antitumor activity in mice.
• Lenalidomide enhanced CAR T-cell immune functions, including cytotoxicity, memory, cytokine production, and immune synapse formation.
• Lenalidomide improved antitumor activity and persistence of adoptively transferred CAR T cells in vivo.

Conclusions:

• Lenalidomide improves the anti-multiple myeloma properties of CS1-directed CAR T cells.
• The findings support a planned clinical trial combining lenalidomide with engineered T cells for relapsed myeloma.