Increased NFAT activity with dual CAR stimulation in CD19xCD22 CAR T-cells is associated with decreased exhaustion and improved survival
Stimulation of both CAR molecules in a CD19xCD22 bicistronic CAR construct impacts downstream signaling events within the CAR T-cell and subsequently drives a more efficacious in vivo response with evidence of decreased exhaustion in persisting cells. These data suggest that bicistronic CAR platforms have the potential to not only target two antigens to prevent antigen-modulated escape but can be engineered to improve multiple facets of CAR T-cell biology, such as mitigating exhaustion, thereby overcoming multiple mechanisms known to drive relapse in current CAR T-cell therapies.
Authors
- Terry J. Fry (ORCID: https://orcid.org/0000-0001-8044-5226)
- Alexander W. Rankin (ORCID: https://orcid.org/0000-0002-6089-9279)
- Catherine Pham‐Danis
- Amanda J Novak (ORCID: https://orcid.org/0009-0009-8780-7395)
- Etienne Danis (ORCID: https://orcid.org/0000-0002-5651-8111)
- M. Eric Kohler (ORCID: https://orcid.org/0000-0002-1181-0418)
Institutions
- Nationwide Children's Hospital (US)
- Center for Cancer and Blood Disorders (US)
- University of Colorado Cancer Center (US)
- University of Colorado Anschutz Medical Campus (US)
- The Ohio State University (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1136/jitc-2025-011971
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Leukemia and Lymphoma Society
- CureSearch for Children's Cancer
- National Institutes of Health
- Cancer Center, University of Colorado
- National Cancer Institute