Aptamer-T Cell Targeted Therapy for Tumor Treatment Using Sugar Metabolism and Click Chemistry

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor (CAR) T-cell therapy is effective for B cell malignancies but carries risks like genotoxicity.
• There is a critical need for safer, tumor-targeted immunotherapies with reduced side effects.

Purpose of the Study:

• To develop and evaluate a nonviral, aptamer-T cell targeted strategy for cancer immunotherapy.
• To assess the efficacy and safety of aptamer-conjugated T cells in targeting and eliminating tumor cells.

Main Methods:

• Conjugation of tumor-specific ssDNA aptamers to CD3+ T cells using N-azidomannosamine (ManNAz) and click chemistry.
• In vitro and in vivo evaluation of aptamer-T cell targeting specificity and anti-tumor activity in mouse models.
• Assessment of T cell activation markers and cytotoxic molecule expression.

Main Results:

• Aptamer-T cells specifically targeted and bound to tumor cells in vitro and in vivo.
• Adoptive transfer of aptamer-T cells resulted in significant tumor volume regression.
• Enhanced T cell cytotoxicity, with increased expression of perforin, granzyme B, CD107a, CD69, and FasL, was observed in the tumor microenvironment.
• Aptamer-T cells demonstrated superior antitumor effects compared to anti-PD1 monoclonal antibody treatment, with synergistic effects when combined.

Conclusions:

• The nonviral aptamer-T cell strategy is a feasible and effective approach for tumor-targeted immunotherapy.
• This method offers a promising alternative to viral-based CAR-T cell therapies with reduced genotoxicity risks.
• Further research into aptamer-T cell therapy could lead to improved cancer treatment outcomes.