In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer

Authors

Lingeng Lu, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; Yale Cancer Center, Yale University, New Haven, CT 06510, USA. Electronic address: lingeng.lu@yale.edu.Follow
Wenxue Ma, Department of Medicine, Moores Cancer Center and Sanford Stem Cell Clinical Center, University of California San Diego, La Jolla, CA 92093, USA.
Caroline H. Johnson, Yale Cancer Center, Yale University, New Haven, CT 06510, USA; Department of Environmental Health Science, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.Follow
Sajid A. Khan, Yale Cancer Center, Yale University, New Haven, CT 06510, USA; Department of Surgery, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.Follow
Melinda L. Irwin, Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; Yale Cancer Center, Yale University, New Haven, CT 06510, USA.
Lajos Pusztai, Yale Cancer Center, Yale University, New Haven, CT 06510, USA; Department of Medical Oncology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.Follow

Document Type

Article

Publication Title

Vaccine

Abstract

Somatic mutation-derived neoantigens are associated with patient survival in breast and ovarian cancer. These neoantigens are targets for cancer, as shown by the implementation of neoepitope peptides as cancer vaccines. The success of cost-effective multi-epitope mRNA vaccines against SARS-Cov-2 in the pandemic established a model for reverse vaccinology. In this study, we aimed to develop an in silico pipeline designing an mRNA vaccine of the CA-125 neoantigen against breast and ovarian cancer, respectively. Using immuno-bioinformatics tools, we predicted cytotoxic CD8 T cell epitopes based on somatic mutation-driven neoantigens of CA-125 in breast or ovarian cancer, constructed a self-adjuvant mRNA vaccine with CD40L and MHC-I -targeting domain to enhance cross-presentation of neoepitopes by dendritic cells. With an in silico ImmSim algorithm, we estimated the immune responses post-immunization, showing IFN-γ and CD8 T cell response. The strategy described in this study may be scaled up and implemented to design precision multi-epitope mRNA vaccines by targeting multiple neoantigens.

First Page

2073

Last Page

2083

DOI

10.1016/j.vaccine.2023.02.048

Publication Date

3-17-2023

Recommended Citation

Lu, Lingeng; Ma, Wenxue; Johnson, Caroline H.; Khan, Sajid A.; Irwin, Melinda L.; and Pusztai, Lajos, "In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer" (2023). Surgery. 210.
https://scholar.bridgeporthospital.org/surgery/210

Identifier

36813666 (pubmed); NIHMS1877854 (mid); PMC10064809 (pmc); 10.1016/j.vaccine.2023.02.048 (doi); S0264-410X(23)00183-4 (pii)