High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen...

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• CD16-chimeric antigen receptor (CAR) T cells target therapeutic antibodies via their Fc-portion, enabling selective antigen targeting.
• Optimal CD16-CAR design and antibody partners for enhanced efficacy remain under investigation.
• This study hypothesizes that high-affinity CD16 variants and Fc-engineered antibodies will improve CD16-CAR T cell effectiveness.

Purpose of the Study:

• To evaluate the efficacy of different CD16-CAR T cell designs and antibody partners.
• To determine if high-affinity CD16 variants and Fc-engineered antibodies enhance anti-tumor activity.
• To assess the impact on T cell proliferation, activation, and cytotoxicity.

Main Methods:

• Co-culture of CD16-CAR T cells (wild-type and variants) with cancer cell lines (Panc-1, Raji, A375).
• Treatment with anti-CD20, anti-MCSP, wild-type, or glycoengineered antibodies.
• In vitro assessment of T cell proliferation, activation, and cytotoxicity.

Main Results:

• The CD16 158V variant of CD16-CAR T cells demonstrated increased cytotoxic activity against all tested cancer cells when combined with wild-type antibodies.
• Glycoengineered antibodies boosted CD16-CAR T cell activity compared to wild-type antibodies, regardless of CD16 polymorphisms.
• Synergistic effects were observed when combining glycoengineered antibodies with the CD16-CAR 158V variant, improving all measured endpoints.

Conclusions:

• CD16-CAR T cells utilizing the high-affinity CD16 variant 158V show potent anti-tumor efficacy.
• The combination of Fc-engineered antibodies with high-affinity CD16-CAR T cells offers a promising strategy for cancer therapy.
• This approach leads to significant improvements in T cell-mediated anti-tumor responses.