CAR T cells boosted to better attack solid tumors and resist PD-1 suppression

CD28-KITv CAR T cells with PD-1 dominant negative receptor

NIH-funded research Sloan-Kettering Inst Can Research · NIH-11457454

Engineered immune cells that target mesothelin and resist tumor suppression for people with solid tumors such as pleural mesothelioma.

Quick facts

Grant typeNIH-funded research
Study typeNIH-funded research
Funding institutionSloan-Kettering Inst Can Research NIH-funded
Lab location1 site (New York, United States)
Project IDNIH-11457454 on NIH RePORTER

What this research studies

You would receive CAR T cells engineered to bind mesothelin, a protein present on many solid tumors. The cells combine CD28 costimulation with a KITv change to boost IFNγ signaling and include a built-in PD‑1 dominant negative receptor so they keep functioning in an immune-suppressive tumor environment. These CAR T cells can be given regionally (for example directly into the chest for pleural disease) to improve tumor infiltration and avoid lung trapping. The team has already treated patients with related CAR designs and is expanding the approach to make responses stronger and more durable.

Who could benefit from this research

Good fit: Ideal candidates are people with mesothelin-expressing solid tumors such as malignant pleural mesothelioma who are eligible for cellular therapy and can undergo regional delivery.

Not a fit: Patients whose tumors lack mesothelin expression or who cannot receive cell therapy or regional infusion are unlikely to benefit.

Why it matters

Potential benefit: If successful, this could produce stronger, longer-lasting CAR T responses against mesothelin-positive solid tumors and potentially improve survival.

How similar studies have performed: Early clinical work at this center using mesothelin-targeted CD28 CARs with PD‑1 dominant negative receptors has shown imaging responses, signs of increased survival, and manageable toxicities.

Where this research is happening

New York, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.