Circular Bispecific Aptamer-Mediated Artificial Intercellular Recognition for Targeted T Cell Immunotherapy.

Area of Science:

• Immunotherapy
• Biotechnology
• Oncology

Background:

• Adoptive T cell immunotherapy, including CAR T cell therapy, is effective for blood cancers but faces challenges with solid tumors due to complex engineering and side effects.
• Solid tumors often have low expression of tumor-specific antigens, limiting the efficacy of current T cell therapies.
• Existing T cell therapies require extensive ex vivo manipulation, which is time-consuming and costly.

Purpose of the Study:

• To develop a simplified T cell immunotherapy strategy that overcomes the limitations of current approaches, particularly for solid tumors.
• To create a method that enables T cells to recognize and accumulate at tumor sites before in situ activation.
• To establish a versatile platform for cancer treatment adaptable to different cancer types.

Main Methods:

• A "recognition-then-activation" strategy was employed, utilizing circular bispecific aptamers (cb-aptamers) for T cell-tumor cell binding.
• Naïve T cells were directed to cancer cells via cb-aptamers, facilitating T cell accumulation at the tumor site.
• In situ activation of accumulated T cells was achieved using commercial CD3/CD28 T cell activator beads.

Main Results:

• The strategy successfully mediated artificial intercellular recognition between T cells and cancer cells.
• T cells were effectively accumulated at the tumor site through cb-aptamer binding.
• In situ activation led to specific cancer cell killing without complex ex vivo engineering.

Conclusions:

• The "recognition-then-activation" strategy offers a simplified approach to T cell immunotherapy, avoiding complicated cell engineering.
• This method demonstrates potential for treating solid tumors by enabling targeted T cell accumulation and activation.
• The adaptability of aptamers allows for potential application in treating a wide range of cancers.