mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor T cells (CAR-Ts) show promise in cancer treatment.
• Cancer cells can evade destruction by losing targeted antigens, necessitating strategies to overcome this resistance.
• Targeting multiple antigens with multiple CARs is one proposed solution, but can be complex.

Purpose of the Study:

• To present a less cumbersome alternative to multi-CAR strategies: anti-tag CARs (AT-CARs).
• To develop and characterize novel AT-CARs utilizing the monomeric streptavidin 2 (mSA2) biotin-binding domain.
• To evaluate the efficacy of mSA2 CAR T cells in targeting and eliminating cancer cells.

Main Methods:

• Engineered human T cells to express mSA2 CARs with CD28-CD3ζ and 4-1BB-CD3ζ signaling domains.
• Activated mSA2 CAR T cells using plate-immobilized biotin and tumor cells coated with biotinylated antibodies (anti-CD19, anti-CD20).
• Assessed CAR T cell activation, cancer cell lysis, and interferon-gamma (IFNγ) production.

Main Results:

• mSA2 CAR T cells demonstrated activation in response to biotin and biotinylated antibody-coated tumor cells.
• Effective lysis of cancer cells and IFNγ production were observed in an antibody dose-dependent manner.
• The mSA2 CAR functions as a universal AT-CAR system.

Conclusions:

• The developed mSA2 CAR offers a versatile and potentially simpler alternative for CAR T-cell therapy.
• This universal AT-CAR can be combined with various biotinylated tumor-specific antibodies.
• This approach holds potential for targeting diverse cancer types by adapting the antibody component.