Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy

Area of Science:

• Immunotherapy
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR)-T cell therapy shows promise for hematological cancers but faces challenges in treating solid tumors.
• CD105 is upregulated on neoangiogenic endothelial and cancer cells, making it a potential therapeutic target for solid tumors.

Purpose of the Study:

• To develop and evaluate nanobody-based CAR-T cells for targeting CD105 to treat solid tumors.
• To assess the in vitro and in vivo efficacy of CD105-specific CAR-T cells.

Main Methods:

• Generated CD105-specific nanobodies and engineered anti-CD105 CAR-T cells using CRISPR/Cas9 technology.
• Evaluated CAR-T cell activation, proliferation, cytokine production, and cytotoxic activity against CD105+ target cells in vitro.
• Assessed the in vivo anti-tumor efficacy in a human tumor xenograft model using NOD/SCID mice.

Main Results:

• Anti-CD105 CAR-T cells exhibited activation, proliferation, cytokine production, and specific killing of CD105+ target cells in vitro.
• In vivo treatment with anti-CD105 CAR-T cells significantly inhibited tumor growth, reduced tumor weight, and prolonged survival in tumor-bearing mice.
• Demonstrated the potential of nanobody-based CAR-T cells as an antitumor agent in human tumor xenograft models.

Conclusions:

• Nanobody-based CAR-T cells engineered via CRISPR/Cas9 targeting CD105 represent a promising strategy for solid tumor treatment.
• This approach shows potential for enhancing the efficacy of CAR-T cell immunotherapy against solid cancers.