Combining the advantages of CAR and TCR, innovative cell therapy for solid tumors steps into the cli

Triumvira Immunologics stated in September that it had completed the first patient dosage in a clinical trial of its TAC-T cell therapy, TAC01-HER2, for the treatment of HER2-positive solid tumors. Triumvira is researching novel autologous and allogeneic T cell therapies that take advantage of T cells' natural biology to treat patients with solid and fluid tumors. The company's proprietary T-cell antigen connector (TAC) platform works differently than CAR-T and TCR-T cell treatments to trigger natural T-cell activity.

TAC is a hybrid molecule made up of multiple protein structural domains, one of which can bind to antigens produced on the tumor surface. Unlike tumor chimeric antigen receptor (CAR), TAC lacks an intracellular co-stimulatory domain and activates T cells by attaching to the TCR on the T cell surface via the TCR's natural regulatory mechanism. The benefit of this design is that the TCR's self-regulatory mechanism is intact, allowing TAC-T cells to be activated only when necessary. One of the key causes of T cell fatigue is the constant activation of CAR produced by CAR-T cells. This approach is predicted to prolong the survival of TAC-T cells and improve their ability to fight cancer.

In contrast to TCR-T cells, TAC binding to antigen is not dependent on antigen major histocompatibility complex (MHC) presentation, providing flexibility in terms of the type of antigen targeted.

Benefits:

Since TAC itself does not possess signaling ability, T-cell activation is mediated only by endogenous natural TCRs, allowing natural activation of TCR signaling ability, thus, there are no toxic side effects such as CRS and neurotoxicity caused by CAR-T cells.

TAC, on the other hand, leverages the anti-cancer potential of intact T cells while maintaining the cells' innate control and safety mechanisms, perhaps offering greater modulation of T cell activation. TAC compounds can be refined and fine-tuned for individual tumor types by using specific tumor targets and additional extracellular or intracellular components.

TAC, in some ways, resembles a "bridge" between tumor antigen and TCR, utilizing the natural mechanisms of TCR while avoiding the limitations of major MHC, allowing for the development of better therapeutic agents in a broader range of patients with solid tumors and hematologic cancers.

TAC technology was developed by Triumvira to optimize the shortcomings of CARs and TCRs by culturing intact natural T cell receptors to genetically modify T cells and steer these T cells to target cancer antigens, ultimately triggering tumor cell death.

This clinical trial will enroll about 70 patients with HER2-positive metastatic, advanced, or unresectable solid tumors to assess the safety, tolerability, and effectiveness of TAC01-HER2.

"Despite breakthroughs in CAR-T cell therapy for hematologic malignancies, there is still a substantial number of patients with solid tumors who require safe and effective therapies." "The initiation of this clinical trial is a major milestone for Triumvira and a chance to produce clinical proof-of-concept for our TAC technology," stated Dr. Paul Lammers, President and CEO of Triumvira.

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