Prostate Cancer Antigen Presentation by HLA-E as a New Target Mechanism for Immunotherapy
Abstract
We investigate a new paradigm for vaccines and immunotherapies of prostate cancer (PCa). We demonstrate that strain 68-1 rhesus cytomegalovirus (RhCMV)-expressing tumor antigens elicit broad CD8+ T cell responses to epitopes presented by nonpolymorphic major histocompatibility complex (MHC)-E molecules instead of polymorphic, classical MHC-Ia. Due to the high conservation of MHC-E we were able to show that human PCa cell lines and human primary tumor cells stimulate MHC-E-restricted CD8+ T cells elicited in rhesus macaques (RM) by 68-1 RhCMV expressing prostate acid phosphatase (PAP). We began identifying T cell receptors (TCRs) recognizing PAP-derived peptides presented by MHC-E and characterizing such TCRs. Since MHC-E is non-polymorphic, unlike classical MHC type I molecules, TCRs expressed by MHC-E-restricted T cells are not limited to a given MHC-I but can be universally employed regardless of the MHC-type thus enabling the development of a universal T-cell based immunotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1152407
Entities
People
- Ashutosh Kumar Tewari
- Ben Bimber
- Klaus Frueh
- Louis J Picker
- Nina Bhardwaj
- Scott G. Hansen
- Sujit S Nair
Organizations
- Oregon Health & Science University