NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Adoptive T cell therapies (ACTs) show promise in cancer immunotherapy.
• Personalized neoantigen-based ACTs offer exquisite tumor specificity.
• Recent FDA approval of TIL therapy highlights advancements in cell-based cancer treatment.

Purpose of the Study:

• To establish and characterize NEO-STIM, an ex vivo process for generating neoantigen-specific T cell responses.
• To identify critical parameters for priming and expanding potent T cell responses against personalized neoantigens.
• To evaluate the safety and efficacy of this novel ACT approach in a first-in-human clinical trial.

Main Methods:

• Development of the NEO-STIM ex vivo induction process.
• Systematic generation of T cell responses against personalized neoantigens from autologous peripheral blood.
• Characterization of drug products comprising mutant-reactive, polyfunctional, and cytotoxic CD8+ and CD4+ T cells.
• Monitoring of T cell responses in tumor and blood post-infusion in a clinical trial (NCT04625205).

Main Results:

• The NEO-STIM process successfully primes and expands pre-existing memory and de novo CD8+ and CD4+ T cell responses.
• Generated T cells exhibit polyfunctional, cytotoxic activity and recognize autologous tumor material.
• Post-infusion, T cell responses were detected in patient tumor and blood, displaying activated/exhausted and cytotoxic phenotypes.
• A first-in-human clinical trial validated the proof-of-concept for this ACT approach.

Conclusions:

• The NEO-STIM process is an effective method for generating potent neoantigen-specific T cell therapies.
• This personalized ACT approach demonstrates potential for treating solid tumors.
• Continued development and clinical evaluation of NEO-STIM are warranted.