Engineered Adoptive Cell Therapies

Patients eligible for clinical trials with ACTengine® product candidates have a portion of their white blood cells collected using a well-established process called leukapheresis, a procedure in which a fraction of the white blood cells of a patient is extracted from their peripheral blood. These white blood cells are transferred to a manufacturing facility where peripheral blood mononuclear cells (“PBMCs”), which are a subset of white blood cells, are isolated from the leukapheresis product. PBMCs or a selected subset of T cells (e.g. CD8+ T cells) is the starting point of the ACTengine® manufacturing process. T cells contained within PBMCs are activated and subsequently mixed with a lentiviral vector which introduces the genes encoding the target specific TCR into the T cells. These genetically engineered T cells are expanded in the presence of a cytokine mixture. All in all, the total ACTengine® manufacturing time is ~1 week. The ex vivo expanded T cells are concentrated and frozen before undergoing quality control release testing. The resulting cell product can be stored frozen long-term until the patient is ready to receive the infusion.

Enhancement Strategies

Immatics’ latest proprietary ACTengine® manufacturing processes are designed to generate cell product candidates within a short manufacturing window and deliver highly proliferative T cells, with the capability to infiltrate the patient’s tumor and function in a challenging solid tumor microenvironment. Immatics is actively investigating multiple next-generation enhancement strategies to render T cells even more potent to combat solid tumors. For advanced-stage clinical trials and commercial supply, manufacturing processes are planned to be further optimized to ensure a robust manufacturing capability incorporating functionally closed and automated manufacturing systems as well as the use of serum free, chemically defined media.

Immatics’ T cell products are manufactured by Immatics personnel at the UTHealth Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in a state-of-the-art cGMP facility exclusively used by Immatics in Houston, Texas.


A TCER® consists of three distinct elements:

Immatics’ TCER® molecules can be produced and purified utilizing established processes to manufacture antibodies.

Immatics’ TCER® scaffold is the result of a campaign to engineer and evaluate various molecular scaffolds incorporating binding domains derived from affinity and stability enhanced TCRs and from T cell recruiting antibodies, respectively. The TCER® architecture, in Immatics’ in vitro testing, proved to be superior to other tested scaffolds with respect to preclinical efficacy, stability and physio-chemical properties, so called “developability”. TCER® molecules can readily be expressed in CHO-cells with titers comparable to antibody-based biologics. The TCER® protein can be purified using common chromatographic techniques and size-exclusion-chromatography, facilitating the cGMP-compliant manufacturing in established plants.

The manufacturing development phase of IMA401 TCER® is ongoing and includes cell line development, upstream and downstream process development, GMP production, fill and finish, release testing, storage and stability testing.