Session V — Lifetime Achievement: Panel Discussion

Origin Stories from the CAR-T Pioneers

Sadelain and June on how CD19 CAR-T actually got built, what nearly killed it, and what comes next.

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Was CD19 CAR an Obvious Bet?

No. Sadelain’s original goal was T-cell signaling studies in primary T cells, not a cancer drug. CD19 was chosen on lineage biology (expression level, homogeneity) — and bonus: B-cell depletion dodges anti-CAR immunity.

What Nearly Killed the Field

• FDA refused lymphodepleting conditioning for the first trial (“two therapies”) → CAR-T infused without conditioning → nothing happened → MSK invisible for years
• First patient under new protocol died day 5 — trial on hold for a year
• June: mice never showed CRS — a human-only toxicity the field learned the hard way
• Both unable to get NIH funding for years; philanthropy bridged the gap

What’s Next (5–10 Years)

• Sadelain: Convincingly treated solid tumor within 5 years; if immune reset holds, “one-and-done” autoimmunity therapy is a game-changer; CAR-Tregs for diabetes, senolytic CAR-Ts
• June: Cell therapy is a platform — expect engineered stem cells, macrophages, NK cells; bottleneck is engineering (scaling, off-the-shelf, cost), not biology

Lessons for Trainees

1. Vision arrives late — transformative targets emerge from solving tooling problems
2. Expect your field not to believe you
3. Animal models will mislead you about toxicity
4. Regulatory headwinds can be rate-limiting
5. Think platform, not product