The idea of a chimeric antigen receptor (CAR) is to combine specific MHC-independent surface antigen recognition with the ability to activate an immune cell, e.g. a T cell. The general design of a CAR comprises an extracellular domain for antigen recognition, a transmembrane domain as well as costimulatory and signaling domains to transmit the activating signal. Expressed on immune cells, CARs mediate antigen specific effector cell activation and target cell lysis.
Limitations of conventional CAR-T :
Despite tremendous clinical success in B-cell malignancies, broader application of CAR-T is limited in terms of safety and efficacy by the inability to finely tune CAR-T function quantitatively and qualitatively, the appearance of resistance by antigen evasion due to monovalent selection pressure and the lack of safe and exclusive tumor surface antigens to discriminate between healthy and cancerous tissue.
One Solution :
To address the limitations of conventional CAR-T technology, we have developed the adapter CAR-T cell (AdCAR-T) system. By splitting antigen recognition and CAR-T activation, introducing adapter molecules, the system allows precise quantitative (on-/off-switch) as well as qualitative (change and combine target antigens) regulation of CAR-T activity. Moreover, AdCAR-T can function as an "OR"gate, allowing simultaneous or sequential multiple targeting, as well as an "AND"gate, capable to identify and differentially lyse target cells based on complex antigen expression profiles.
(Ad)CAR-T vs. solid Tumors:
Besides safety concerns and antigen loss, CAR-T activity against solid tumors is significantly hampered by immune evasive mechanisms within the tumor microenvironment (TME). To improve CAR-T function by evidence-based engineering, a deep understanding of the cellular composition of as well as specific immune evasive signatures in the TME is essential.
We apply cutting-edge single cell spatial proteomics by ultra-high content imaging to decipher individual immune evasive signatures in primary patient samples as well as complex humanized PDX models.
We are proud to announce that AdCAR-T technology has been developed and licensed in close collaboration with Miltenyi Biotec, Bergisch Gladbach.