Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR, 97239, USA.
Genes Immun. 2023 Aug;24(4):194-199. doi: 10.1038/s41435-023-00212-z. Epub 2023 Jul 13.
With the improvement of treatment options, multiple myeloma related life expectancy has been prolonged, but the disease remains largely incurable. Immunotherapy is a growing field that shows promise in advancements for treatment, and recent work has demonstrated an opportunity to use immune receptor, complementarity determining region-3 (CDR3)-candidate antigen chemical complementarity scores to identify survival distinctions among subgroups of patients. Here, we have applied the complementarity scoring algorithm to identify multiple myeloma related, CDR3-cancer testis antigen (CTA) relationships associated with survival distinctions. Furthermore, we have overlapped these immune receptor features with a previous study that showed a dramatic survival distinction based on T-cell receptor, V- and J-gene segment usage, HLA allele combinations, whereby 100% of the patients in certain combination groups had no mortality related to multiple myeloma, during the study period. This overlap evaluation was consistent with the idea that there are likely considerable constraints on productive TRB-antigen-HLA combinations but more flexibility, and unpredictability, for the TRA-antigen-HLA combinations. Also, the approaches in this reported indicated the potential importance of the CTA, IGSF11, as a multiple myeloma antigen, an antigen previously, independently considered as a vaccine candidate in other settings.
随着治疗选择的改善，多发性骨髓瘤相关的预期寿命已经延长，但该疾病仍然基本上无法治愈。免疫疗法是一个不断发展的领域，在治疗进展方面显示出前景，最近的工作表明有机会利用免疫受体、互补决定区 3（CDR3）-候选抗原化学互补评分来识别患者亚组之间的生存差异。在这里，我们应用了互补评分算法来识别与生存差异相关的多发性骨髓瘤相关的 CDR3-癌症睾丸抗原（CTA）关系。此外，我们还将这些免疫受体特征与之前的一项研究进行了重叠，该研究表明基于 T 细胞受体、V 和 J 基因片段使用、HLA 等位基因组合的显著生存差异，在研究期间，某些组合组的 100%患者与多发性骨髓瘤无关死亡率。这种重叠评估与以下观点一致，即 productive TRB-antigen-HLA 组合可能存在相当大的限制，但对于 TRA-antigen-HLA 组合，则具有更大的灵活性和不可预测性。此外，本报告中所述的方法表明 CTA、IGSF11 作为多发性骨髓瘤抗原的重要性，该抗原以前在其他环境中被独立认为是疫苗候选物。
