Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity
Children's Hospital of Philadelphia · Allen Institute · +7 more institutions
Abstract
Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of the antigen recognized by the CAR poses a major obstacle. We found that in vivo vaccine boosting of CAR T cells triggers the engagement of the endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells. This process was accompanied by shifts in CAR T metabolism toward oxidative phosphorylation (OXPHOS) and was critically dependent on CAR-T-derived IFN-γ. Antigen spreading (AS) induced by vaccine-boosted CAR T enabled a proportion of…
Citation impact
- FWCI
- 42.86
- Percentile
- 100%
- References
- 90
Authors
17- LMLeyuan MaCorresponding
Children's Hospital of Philadelphia, Allen Institute, Koch Institute for Integrative Cancer Research At MIT, University of Pennsylvania
- AHAlexander Hostetler
Allen Institute, Koch Institute for Integrative Cancer Research At MIT
- DMDuncan M. Morgan
IIT@MIT, Allen Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- LMLaura Maiorino
Allen Institute, Koch Institute for Integrative Cancer Research At MIT
- ISIna Sulkaj
Allen Institute, Koch Institute for Integrative Cancer Research At MIT
Topics & keywords
- Biology
- Antigen
- Chimeric antigen receptor
- Priming (agriculture)
- Immunology
- Immune system
- Tumor antigen
- Tumor microenvironment
- Good health and well-being