Michel Sadelain

Founding director of the Columbia Initiative in Cell Engineering and Therapy (CICET), previously Center for Cell Engineering at Memorial Sloan Kettering. Architect of the second-generation CAR and the scFv-based CAR design. Coined the term “CAR” (2003) and “living drugs.” Lifetime Achievement lecture at Session V.

Key Contributions

• Developed retroviral methods for gene transfer into primary T cells (not leukemia lines) — the essential unlock
• Showed that zeta-only CARs → activation-induced cell death in real T cells → invented second-generation dual-signaling CARs (CD28/CD3-zeta)
• Chose CD19 over the more famous CD20 on lineage biology: higher expression, better homogeneity
• First CD19 CAR-T patient infused at MSK: June 2007
• Treated >500 patients with in-house CAR-T cells at MSK

Three New CAR Designs

1XX — Calibrated signaling

• Single live ITAM outperforms wild-type zeta on durability; durable responses at 10 million cells (CRISPR knock-in to TRAC locus)

HIT — HLA-Independent T-cell receptors

• 10–50× lower antigen-density threshold; solves antigen-low escape (Science, 2026)

Pre-TCR Signaling

• Borrows thymocyte expansion logic; extreme potency at low cell doses in GBM (Cell, 2026)

Design Principles

• Calibrate, don’t maximize
• Sensitivity is a design parameter
• Pick targets on lineage biology, not fame
• Steal from developmental biology

“In mastering T cells in the world of medicine, we now have a third modality… immune engineering — creating cells with new, super-physiological properties.”