CONVERTER CAR
- CONVERTER CAR platform with CTC28 technique
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Tumor cells have strategies to avoid attack from the patient’s immune system. One of them is to strengthen the immune checkpoints such as CTLA-4 and PD-1/PD-L1. Thus, there are some efforts to combine CAR-T cell therapy and the immune checkpoint inhibitors. However, the immune checkpoint inhibitors activate all the T cells in patients including autoreactive T cells as well as tumor-specific T cells, which leads to autoimmune adverse side effects.
CONVERTER CAR technique of TiCARos enables selective inhibition of CTLA4 only in tumor-specific CAR-T cells without affecting other T cells in patient’s blood. CTLA4 has been known as a potent T cell inhibiting receptor. Thus, other CTLA4-inhibiting strategy such as neutralizing antibodies elicits strong autoimmune side effects. By selective inhibition of CTLA-4 only in CAR-T cells potentiates CAR-T activity without serious autoimmunity.
In the pre-clinical efficacy tests in mice, the CAR-T cells generated using CONVERTER CAR technique showed superior therapeutic efficacy over a commercialized 2nd generation CAR-T at the dosage where the commercialized CAR-T product shows unsatisfactory efficacy.
- CTC28 T cell – Strengthened T cells
- T cell activity is enhanced by replacing the intracellular inhibitory domain of CTLA4, an inhibitory immune checkpoint receptor, with the stimulatory domain of CD28, an immune-stimulating receptor. Thus, this technique converts a negative signal for T cells to a positive signal, resulting in T cell hyperactivation.
