Technology & Science

Adoptive immunotherapy involves the redirection of white blood cells to attack cancers

Adoptive immunotherapy is achieved by: (i) the extraction of T cells from patients, followed by (ii) the genetic engineering of cells with a T cell Antigen Coupler (TAC), a molecular construct that guides T cells selectively to tumor cells, (iii) expansion of engineered T cells in the lab, then (iv) re-administrating to the patient where these TAC-T cells will find and bind to the cancer cells, and then destroy them. The TAC technology builds on recent findings in immune T cell biology and has the potential to produce therapies that are more effective and safer than existing T cell approaches.

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TAC technology co-opts natural biology

The TAC is designed to co-opt the natural immune defense mechanisms of T cells, a type of white blood cell that is critical in ridding the body from abnormal and cancerous cells in healthy individuals. In cancer patients, these T cells frequently fail to either recognize or effectively engage cancer cells.

TAC is a hybrid molecule comprising multiple protein domains to combine tumor targeting abilities with the T cell’s own activation machinery. Once integrated into patient-derived T cells, one domain facilitates tumor cell recognition by binding to a tumor-specific target and a second domain connects the TAC molecule to the endogenous, natural T cell receptor (TCR). The TAC molecule is anchored in the membrane via the CD4 co-receptor domain, which adds co-receptor functionality to TAC. Through the combination of tumor target and TCR binding ability together with co-receptor integration, TAC leads to natural activation of TCR signaling pathways and, consequently, T cell-mediated killing of tumor cells.

TAC technology co-opts natural biology

The TAC is designed to co-opt the natural immune defense mechanisms of T cells, a type of white blood cell that is critical in ridding the body from abnormal and cancerous cells in healthy individuals. In cancer patients, these T cells frequently fail to either recognize or effectively engage cancer cells.

TAC is a hybrid molecule comprising multiple protein domains to combine tumor targeting abilities with the T cell’s own activation machinery. Once integrated into patient-derived T cells, one domain facilitates tumor cell recognition by binding to a tumor-specific target and a second domain connects the TAC molecule to the endogenous, natural T cell receptor (TCR). The TAC molecule is anchored in the membrane via the CD4 co-receptor domain, which adds co-receptor functionality to TAC. Through the combination of tumor target and TCR binding ability together with co-receptor integration, TAC leads to natural activation of TCR signaling pathways and, consequently, T cell-mediated killing of tumor cells.

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Designing safe and more effective T cell therapy

Because TAC does not have any signaling capacity by itself, T cell activation is solely mediated by the endogenous, natural TCR. Thus, TAC takes advantage of the full T cell anti-cancer potential while retaining the cell’s natural control and safety mechanisms.

The TAC molecule can be customized with specific tumor targeting and other extra- or intracellular moieties, providing opportunities for optimizing and finetuning toward particular tumor types. TAC is currently being developed for autologous (patient-derived) applications and has the potential for allogeneic (“off the shelf”, donor-derived) applications.

TAC technology demonstrates superiority in preclinical models

Triumvira has extensively tested the TAC technology in preclinical studies and demonstrated that TAC T cells – unlike CAR-Ts – lack tonic signaling, carry markers of memory T cells, and effectively invade solid tumors. These characteristics help to completely eliminate solid tumors, with absence of toxicity in vivo.

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