Explain CAR-T cell therapy and its manufacturing process.

CAR-T (Chimeric Antigen Receptor T-cell) therapy engineers patient's T cells to target cancer. CAR structure: extracellular antigen-binding domain (scFv), hinge, transmembrane domain, and intracellular signaling domains (CD3zeta plus co-stimulatory domains CD28 or 4-1BB). Manufacturing: 1) Leukapheresis - collect patient's blood and isolate T cells. 2) Activation - stimulate T cells with anti-CD3/CD28 beads or antibodies. 3) Transduction - introduce CAR gene using lentiviral or retroviral vectors. 4) Expansion - grow cells in bioreactors (10-14 days) to achieve therapeutic dose. 5) Formulation - cryopreserve and ship to treatment site. 6) Infusion - after lymphodepleting chemotherapy. Challenges: vein-to-vein time (3-4 weeks), manufacturing failures, cytokine release syndrome (CRS), neurotoxicity, cost ($400K+), and resistance. FDA-approved products target CD19 (Kymriah, Yescarta for lymphoma) and BCMA (Abecma for myeloma).