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

Mol Immunol. 2022 Oct:150:58-66. doi: 10.1016/j.molimm.2022.08.001. Epub 2022 Aug 17.


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,, offers a convenient opportunity to identify likely parameters important for immunotherapy considerations and melanoma patient risk stratifications.

Keywords: Electrostatic complementarity scores; Immune biomarkers; Immune receptor CDR3s; MAGE auto-reactivity; MAGEA3/6; Survival distinctions.

MeSH terms

  • Antigens, Neoplasm
  • Complementarity Determining Regions / genetics
  • Humans
  • Immunotherapy
  • Male
  • Melanoma*
  • Neoplasm Proteins / metabolism
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes
  • Vaccines*


  • Antigens, Neoplasm
  • Complementarity Determining Regions
  • MAGEA3 protein, human
  • MAGEA6 protein, human
  • Neoplasm Proteins
  • Receptors, Antigen, T-Cell
  • Vaccines