Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy
Brigham and Women's Hospital · Harvard University · +6 more institutions
Abstract
Immunotherapy with immune checkpoint blockade (ICB) has shown limited benefits in hepatocellular carcinoma (HCC) and other cancers, mediated in part by the immunosuppressive tumor microenvironment (TME). As p53 loss of function may play a role in immunosuppression, we herein examine the effects of restoring p53 expression on the immune TME and ICB efficacy. We develop and optimize a CXCR4-targeted mRNA nanoparticle platform to effectively induce p53 expression in HCC models. Using p53-null orthotopic and ectopic models of murine HCC, we find that combining CXCR4-targeted p53 mRNA nanoparticles with anti-PD-1 therapy effectively induces global reprogramming of cellular and molecular components of the immune…
Citation impact
- FWCI
- 33.83
- Percentile
- 100%
- References
- 42
Authors
14- YXYuling XiaoCorresponding
Brigham and Women's Hospital, Harvard University
- JCJiang Chen
Harvard University, Sir Run Run Shaw Hospital, Massachusetts General Hospital, Zhejiang University
- HZHui Zhou
Brigham and Women's Hospital, Harvard University, Wuhan University
- XZXiaodong Zeng
Brigham and Women's Hospital, Harvard University, Wuhan University
- ZRZhiping Ruan
Harvard University, Massachusetts General Hospital, First Affiliated Hospital of Xi'an Jiaotong University
Topics & keywords
- Immune checkpoint
- Immune system
- Tumor microenvironment
- Cancer research
- Immunosuppression
- Immunotherapy
- Blockade
- Cancer immunotherapy
- Good health and well-being