Immatics is developing Adoptive Cell Therapies, which are designed to leverage the power of T cells to actively infiltrate tumor tissue and kill tumor cells in a specific and serial fashion.
at a glance
Immatics’ clinical product class ACTengine® is a personalized approach in which the patient’s own T cells are genetically modified to express a novel proprietary TCR cognate to one of Immatics’ proprietary cancer targets and are then reinfused. This approach is also known as TCR-T (T cell receptor T cell). The product class ACTallo® is advancing the ACT concept beyond individualized manufacturing and is being developed to generate “off-the-shelf” cellular therapy. ACTolog® is a clinical pilot study for ultra-personalized, multi-target immunotherapy utilizing endogenous (non-genetically engineered) T cells with the goal of paving the way for a next step of enabling a fully engineered multi-TCR-T.
Expanded target space compared to CAR-T
ACTengine® TCR-T targets tumor-associated peptides presented by HLA-molecules on the tumor cell surface. Most relevant solid cancer targets are of intracellular nature and thus only accessible by TCR-based approaches.
TCRs with desirable affinity and specificity
ACTengine® TCRs identified via the XCEPTOR™ TCR discovery and characterized via XPRESIDENT® guided on- and off-target toxicity screening show desirable affinity and high specificity. Immatics’ competitive advantage to other TCR-T approaches is the combination of the most suitable target (via XPRESIDENT®) with the right TCR (via XCEPTOR™).
Active at physiological levels of target expression
Immatics believes that ACTengine® TCR-T products are highly potent and capable of inducing the killing of tumor cells presenting physiological target copy numbers identified by quantitative mass spectrometry and TCR validation.
Immatics’ proprietary short manufacturing process including a significantly shorter manufacturing period and a proprietary cytokine cocktail used to promote T cell expansion in culture is designed to produce younger, less differentiated T cell phenotypes which are associated with better engraftment and in vivo persistence.
Patient recruitment is underway in three first-in-human clinical trials. The clinical trials are investigating safety, tolerability and initial signs of efficacy in patients and are designed to include potential expansion cohorts in the case of initial signs of clinical efficacy. This may enable a fast way forward towards pivotal clinical trials in specific indications.
Early biological data from first patients treated
Initial biological data from the first patients treated in the ACTengine® trials (N=4) suggest a high persistence of target-specific T cells after infusion, already at the first low-dose level, which constitutes approximately 5-10% of Immatics’ anticipated target dose. These target-specific T cells can also be detected in post-treatment tumor biopsies.
There are several reasons why a patient’s own T cells are often not able to protect the body against cancer, such as unavailability of activated tumor antigen specific T cells or insufficient affinity of endogenous target specific TCRs to properly activate the T cell and fight the tumor. Immatics believes that these problems can be overcome by engineering of autologous T cells with a well characterized and potent TCR, an approach used in its ACTengine® program.
ACTengine® is based on genetically engineering a patient’s own T cells with a novel TCR designed to recognize the cancer target identified by Immatics’ XPRESIDENT® platform. If the target of interest is confirmed on a patient’s tumor by the IMADetect™ companion diagnostic device candidate, lentiviral transduction of the patient’s autologous T cells with a target specific exogenous TCR essentially “reprograms” the T cells to attack the tumor. The engineered T cells are then multiplied in vitro and reinfused back into the patient to treat the tumor.
In Immatics’ current ACTengine® clinical trials, infusion of the engineered T cells is preceded by a preconditioning lymphodepleting chemotherapy to activate proliferation, facilitate T cell engrafting and persistence. Post-infusion of the T cell product, low-dose IL-2 is administered for 14 days to further enhance persistence of the adoptively transferred cells.