Adoptive Cell Therapy
Adoptive Cell Therapy (ACT) has the potential to cure cancer. ACT is a treatment that uses natural or engineered T cells to fight cancer.
Immatics and the University of Texas MD Anderson Cancer Center launched Immatics US, Inc in 2015 to become a global leader in ACT for treatment of multiple tumor types. This collaboration leverages Immatics' excellence in immune-oncology and MD Anderson's world leading adoptive cell therapy and clinical oncology expertise, and has received a $19.7 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT).
Immatics has developed three innovative, proprietary approaches to producing Adoptive Cell Therapies: ACTolog®, ACTengine® and ACTallo®. These therapies are directed against targets, which will transform the current landscape of tumor therapy.
ACTolog® is based on the principle of endogenous T-cell therapy pioneered by Professor Cassian Yee, MD. Unlike tumor-infiltrating lymphocytes (TILs), ACTolog® T-cell products are generated from peripheral blood cells with defined target selectivity. Utilizing our proprietary target discovery platform XPRESIDENT®, Immatics has created a warehouse of multiple cancer targets. From this pool, the most suitable targets for each patient’s tumor are identified by analyzing tumor biomarkers. Up to four personalized T-cell products are then manufactured for each patient by isolation, propagation and activation of the patient’s endogenous T cells in vitro. Billions of such activated and specific T cells are then re-infused into the cancer patient to attack the tumor.
ACTolog® combines several innovative features:
- The target antigens have been validated as being naturally presented in various solid tumors by Immatics’ proprietary XPRESIDENT® target discovery platform.
- The selection and manufacture of each patient’s ACTolog® cell therapy product is actively tailored by measuring the relative presence of eight pre-selected and well-characterized patient tumor-specific antigens.
- The ACTolog® approach generates multiple cell therapy products, each directed against a different tumor target. This approach is designed to be effective in the event of tumor escape variants, compared to targeting just one single antigen.
- The ACTolog® manufacturing approach yields T cells with prolonged persistence in the patients's circulation post infusion.
ACTolog® is different from therapies based on tumor-infiltrating lymphocytes (TILs):
- Established and straightforward production from patient's blood
- Definded T cell specificities
- Not limited to tumor types with high mutation rates (such as melanoma)
ACTengine® is based on genetically engineering a patient’s own T cells to express an exogenous T-cell receptor (TCR) upon lentiviral transduction. This approach essentially "reprograms" a patient's T cells to attack tumor cells.
Highly specific exogenous T-cell receptors (TCRs) with optimal affinity are identified via Immatics’ proprietary high-throughput screening (HTS) from natural, human T-cell repertoire.
- Patients are eligible for ACTengine® cell therapy if the target of interest is present on the patients’ tumor as demonstrated by biomarker profile.
- The transduced TCRs recognize the tumor-specific peptides previously identified by XPRESIDENT® and do not require further affinity maturation.
- The engineered T cells are then multiplied outside the body before being infused into the patient.
ACTallo® is based on the genetically engineering allogeneic gamma-delta T cells to express novel and exogenous TCRs. In addition to the specific tumor recognition via the ectopic ("placed") TCR, gamma-delta T cells may demonstrate inherent activity against numerous tumor types.
This apporach delivers “off-the-shelf” T-cell products for rapid treatment of all eligible patients with a specific cancer expressing the target of interest in their tumor. It therefore eliminates the need for personalized manufacturing.
Immatics believes its strategy of developing different types of Adoptive Cell Therapies in combination with the identification of proprietary cancer targets, will deliver a transformative change in the treatment of solid tumors.