Immune Immune 4: Putting the immunotherapy CAR T before the cancer
Jan 23, 2018
Delve into the intricacies of cancer immunotherapy and the revolutionary CAR T cells. Discover how monoclonal antibodies target tumors and the innovative strategies to engineer T cells for better precision. Explore challenges like tumor evasion and the importance of co-stimulatory signals for effective treatment. From engineered kill switches to potential applications beyond cancer, the hosts discuss the future of CAR therapy, including its high costs and healthcare implications. The fascinating intersection of immunology and innovation awaits!
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How CAR T-Cells Work
- CAR T-cells fuse an antibody's targeting domain to a T cell's signaling machinery to retarget T cells against tumors.
- This synthetic chimeric antigen receptor bypasses MHC restrictions and allows high-affinity recognition of native surface antigens.
Tumors Use Immune Checkpoints
- Tumors exploit normal immune "off" signals to suppress T cell killing by upregulating inhibitory ligands.
- Checkpoint inhibitors (anti-CTLA-4, anti-PD-1) block those suppressive signals to restore T cell activity.
Signal One Plus Signal Two Matters
- CAR design requires both antigen recognition and intracellular co-stimulatory signals to avoid T cell anergy.
- Adding co-stimulatory cytoplasmic domains produced second-generation CARs with robust activation and persistence.