Chemical complementarity between tumor resident, T-cell receptor CDR3s and MAGEA3/6 correlates with increased melanoma survival: Potential relevance to MAGE vaccine auto-reactivity. (October 2022)

• Record Type: Journal Article
• Authors: Eakins, Rachel A.; Chobrutskiy, Andrea; Teer, Jamie K.; Patel, Dhruv N.; Hsiang, Monica; Huda, Taha I.; Zaman, Saif; Sexton, Wade J.; Coppola, Domenico; Falasiri, Shayan; Blanck, George; Chobrutskiy, Boris I.
• Is Part Of: Molecular immunology. Volume 150(2022)
• Page Start: 58
• Page End: 66
• Publication Date: 2022-10
• Subjects: AA amino acid -- AJCC American Joint Committee on Cancer -- BLAST Basic Local Alignment Search Tool -- CDR3 complementarity determining region-3 -- CS complementarity score -- CTA cancer testis antigen -- DFS disease-free survival -- HUGO human genome organization -- IR immune receptor -- KM Kaplan-Meier -- OS overall survival -- PCR polymerase chain reaction -- SKCM skin cutaneous melanoma -- SPSS Statistical Package for the Social Sciences -- TCGA the cancer genome atlas -- TCR T-cell receptor -- WXS exome; Electrostatic complementarity scores -- Immune receptor CDR3s -- MAGEA3/6 -- Survival distinctions -- Immune biomarkers -- MAGE auto-reactivity; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.08.001
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: Cancer testis antigens have been of interest as possible targets for cancer immunotherapies. To better understand the opportunities for the use of such immunotherapy targets, we used a chemical complementarity scoring algorithm and an original web tool to establish aspects of electrostatic complementarity of the CTAs, MAGEA3 and MAGEA6, with melanoma specimen resident, T-cell receptor (TCR) complementarity determining region 3 (CDR3) amino acid sequences. Greater electrostatic complementarity between T-cell receptor CDR3 and tumor CTAs MAGEA3/6 was associated with a greater probability of overall survival, for both the cancer genome atlas and Moffitt Cancer Center samples; and was associated with high levels of T-cell cytotoxicity-related gene expression. Most importantly, this approach allowed for the highly efficient screening of specific segments of the MAGEA3/6 antigens which indicated that certain MAGE segments would have either more or less risk of auto-reactivity. In sum, the chemical complementarity algorithm, and its efficient application via the web tool, adaptivematch.com, offers a convenient opportunity to identify likely parameters important for immunotherapy considerations and melanoma patient risk stratifications. Highlights: Linkage of melanoma immune receptor chemistry to cancer testis antigens and survival. Use of a novel web tool for assessing candidate antigens. Immunogenomics dissections of previously failed vaccines, to identify better candidates.