IMMUNOLOGY2026™ Conference Recordings For Attendees-Goal-oriented transgenic TCR-T cell design for efficient cancer immunotherapy

Video Transcription

Video Summary

Sergei Panteliev presented ongoing work on designing goal-oriented TCR T-cells for cancer immunotherapy. He compared three engineering strategies: standard viral transduction, endogenous TCR knockout, and full TCR replacement (“knock-in”). His central finding was that endogenous TCRs can reduce sensitivity through competition and mispairing, limiting tumor-antigen recognition. In short-term assays, knocking out endogenous TCR improved antigen sensitivity, and full replacement performed similarly. But after repeated restimulation, full knock-in cells began to outperform knockout cells.  <br /><br />To study responses at higher resolution, the lab developed a calcium flux imaging assay and used dynamic time warping to cluster single-cell response patterns. This revealed distinct populations: strong responders, weak/oscillatory responders, non-responders, and intermediate responders. Overall, removing endogenous TCR improved both the speed and quality of responses, especially for weak agonists. Panteliev concluded that knockout/knock-in is most useful for long-lived, off-the-shelf products, while viral transduction may still be preferable for smaller-scale or short-term studies.

Meta Tag

Date April 18, 2026 12:45 PM - 1:00 PM

Room 151

Session Technical Innovations for Therapies

Speaker Sergey Panteleev

Track Technological Innovations in Immunology (TECH)

Year 2026

Keywords

TCR T-cells

cancer immunotherapy

endogenous TCR knockout

TCR knock-in

calcium flux imaging

April 18, 2026 12:45 PM - 1:00 PM

151

Technical Innovations for Therapies

Sergey Panteleev

Technological Innovations in Immunology (TECH)

2026