Article Text

Download PDFPDF

372 TAC-T cells persist and remain functional during and after repeated tumor exposure in vitro and in vivo
  1. Heather L MacGregor1,
  2. Suzanna L Prosser1,
  3. Stacey X Xu1,
  4. Kyle MacDonald1,
  5. Aksha Kadri1,
  6. Ritu R Randhawa1,
  7. Swati Shetty1,
  8. Sailaja Pirati1,
  9. Deepika Bhemarasetty1,
  10. Christopher W Helsen1,
  11. Sadhak Sengupta2 and
  12. Andreas G Bader2
  1. 1Triumvira Immunologics, Hamilton, ON, Canada
  2. 2Triumvira Immunologics, Austin, TX, USA


Background T cell antigen coupler (TAC) is a chimeric receptor that redirects T cells (TAC-T) towards surface-expressed tumor antigens to create safe and durable anti-cancer immune responses. The TAC receptor activates T cells by co-opting the endogenous T cell receptor machinery via a CD3ε-specific binding motif and a cytoplasmic co-receptor tail. TAC01-HER2, a first-in-class TAC-T product targeting HER2 (ERBB2), has entered a phase I/II clinical trial. Here, we show that TAC-T cells retain their cytotoxicity capacity during and after repeated tumor challenges in vitro and in vivo.

Methods The robustness of anti-tumor T cell responses were assessed in vitro in a recursive killing assay by repeatedly exposing HER2-specific TAC-T cells to HER2-expressing tumor cells for 11 successive rounds (39 days). T cells were characterized by flow cytometry to correlate T cell phenotypes with anti-tumor activity. In vivo, ongoing tumor control established by a single infusion of TAC-T cells was assessed in a tumor rechallenge experiment. MHC I/II-deficient NSG mice were engrafted subcutaneously with HER2+ tumor cells and rechallenged with the same tumor cell line 28 days later. TAC-T cells were isolated from mice at various time points for phenotypic and functional characterization.

Results TAC-T products controlled tumor cell growth through 11 rounds of tumor cell challenge in vitro. Signs of reduced functionality were observed at round 11, which coincided with the emergence of a dysfunctional phenotype. During in vivo tumor rechallenge experiments, a single infusion of TAC-T cells led to complete clearance of the solid tumor xenograft and protected mice from a second tumor challenge 28 days after adoptive T cell transfer. TAC-T cells recovered from tumor sites at various time points exhibited phenotypic markers of activation, whereas TAC-T cells isolated from blood and spleen appeared to be antigen-experienced cells but lacked markers indicative of chronic activation and exhaustion. TAC-T cells isolated from spleens before and after the rechallenge were able to proliferate and kill tumor cells ex vivo.

Conclusions Here we report evidence that TAC-T cells controlled tumor cell growth through 11 rounds of repeated tumor rechallenge in vitro, protected mice against tumor rechallenge, and demonstrated long-term ex vivo proliferative and cytotoxic capabilities. These data indicate long-lasting T cell persistence and functionality against solid tumors.

Ethics Approval Animal studies performed for the work presented in this abstract were conducted under the Animal Utilization Protocol (AUP) # 20–10-37 and approved by the Animal Research Ethics Committee at McMaster University (Hamilton, ON, Canada).

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.