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.

All clinical T cell products are manufactured by our employees through a multi-year collaboration with the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory at UTHealth (“UTH”) McGovern Medical School in Houston, Texas that provides us exclusive access to several cGMP manufacturing suites. The UTHealth facility is FDA-registered to manufacture cells and tissues for clinical applications in compliance with cGMP and is accredited by the Foundation for Accreditation of Cellular Therapy (“FACT”).


A TCER® consists of three distinct elements:

Immatics’ TCER® molecules are expressed in mammalian CHO cells and can be produced and purified utilizing established processes with titers comparable to antibody-based biologics.

The TCER® architecture was proven to be superior to other scaffolds Immatics tested in terms of preclinical efficacy, stability and physio-chemical properties, so called “developability”. The TCER® protein can be purified using common chromatographic techniques and size-exclusion-chromatography, facilitating the cGMP-compliant manufacturing in established facilities.

The manufacturing development phase of a TCER® compound includes cell line development, upstream and downstream process development,formulation development, development of suitable analytical methods for testing and release, cGMP production, fill and finish, storage and stability testing.