Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression.

One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens. This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data. We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s. Also, we have established gene expression correlations with the high TCR CDR3-CTA chemical complementarities, for Granzyme B, and other immune biomarkers. Overall, for several independent TCR CDR3 breast cancer datasets, the CTA, ARMC3, stood out as a completely novel, candidate antigen based on multiple algorithms with highly consistent approaches. This conclusion was facilitated by use of the recently constructed Adaptive Match web tool.

Pakasticali N ，Chobrutskiy A ，Patel DN ，Hsiang M ，Zaman S ，Cios KJ ，Blanck G ，Chobrutskiy BI ... -  《-》

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

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.

Eakins RA ，Chobrutskiy A ，Teer JK ，Patel DN ，Hsiang M ，Huda TI ，Zaman S ，Sexton WJ ，Coppola D ，Falasiri S ，Blanck G ，Chobrutskiy BI ... -  《-》

TRB CDR3-cancer testis antigen chemical complementarity scoring for identifying productive immune responses in renal cell carcinoma.

Hudock TR ，Barker VR ，Manley BJ ，Chobrutskiy A ，Chobrutskiy BI ，Diaz MJ ，Song JJ ，Blanck G ... -  《-》

An immunoinformatics assessment of the cancer testis antigen, DDX53, as a potential early esophageal cancer antigen.

Cheng P ，Cios KJ ，Varkhedi M ，Barker VR ，Yeagley M ，Chobrutskiy A ，Chobrutskiy BI ，Blanck G ... -  《-》

Chemical complementarity between immune receptor CDR3s and candidate cancer antigens correlating with reduced survival: evidence for outcome mitigation with corticosteroid treatments.

Patel AR ，Patel DN ，Tu YN ，Yeagley M ，Chobrutskiy A ，Chobrutskiy BI ，Blanck G ... -  《-》