Systems Biology Approach for Cancer Vaccine Development and Evaluation

Abstract

Therapeutic cancer vaccines do not hold promise yet as an effective anti-cancer treatment. Lack of efficacy or poor clinical outcomes are due to several antigenic and immunological aspects that need to be addressed in order to reverse such trends and significantly improve cancer vaccines’ efficacy. The newly developed high throughput technologies and computational tools are instrumental to this aim allowing the identification of more specific antigens and the comprehensive analysis of the innate and adaptive immunities. Here, we review the potentiality of systems biology in providing novel insights in the mechanisms of the action of vaccines to improve their design and effectiveness.

From single gene analysis to single cell profiling: a new era for precision medicine

“…Overall, new technical advancements will foster development of ready-to-use chips for easy and rapid screening of vaccines to improve the outcome of vaccinations. Systems vaccinology, that is the global approach applied to vaccinology from discovery of new antigens to evaluation of vaccine efficacy, represents the real turning point for the switch from the "empirical" to the "knowledge-based" age of the vaccinology, enabling the development of even more successful vaccines for preventive as well as therapeutic intervention strategies for cancer immunotherapy [41]. Finally, Sabrina Arena from University of Turin and Candiolo Cancer Institute, Turin (Italy), discussed the clonal cancer evolution as therapeutic target.…”

Exploitation of Cell Mediated Immune Responses to Cancer Immunotherapy

“…This approach, therefore, offers possibility for long-term cancer remission and decreases risk of recurrence by stimulating a long lasting immune guard against the cancer. It is highly selective for the cancer cells and can potentially be tailored to the patient's individual cancer, by the use of tumor-specific mutant antigens which are natural potential candidates for developing personalized cancer-specific vaccines (Circelli et al, 2015;Lacombe, 2016). Manipulation of the immune response has resulted in promising therapies by boosting the ability of the immune system to target cancer, or by limiting the ability of tumors to evade the natural immune response (Finotello & Trajanoski, 2017).…”

“…ACT with tumor-infiltrating lymphocytes (TILs) is an approach where T cells, generally mixtures of CD8+ and CD4+ T cells grown from resected metastatic tumor deposits, are harvested and expanded ex vivo prior to adoptive transfer. This approach attempts to reverse the functional impairment of the tumor-specific T cells that reside within the tumor, and caused by the immune suppressive tumor microenvironment, by growing them prior to the reinfusion in a cocktail of various cytokines and tumor-specific mutant antigens (Circelli et al, 2015). The ability of adoptive immunotherapy to mediate durable tumor regressions in some patients may depend in part upon the fact that many TIL populations contain T cells that recognize multiple neoantigens (Lu & Robbins, 2016;Schumacher & Schreiber, 2015;Yuzhakova et al, 2016) or driver mutations that are essential for carcinogenesis.…”

Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy

“…Provided all the immunological implications related to the cancer disease and the chemotherapy, an experimental validation is needed to prove that adjuvants are equally effective in healthy subjects and cancer patients. For such a reason, taking advantage of an ex vivo multiparametric platform, developed and fully validated by our group [27][28][29][30][31][32][33], we have previously shown that HCC patients who do not undergo chemotherapy and healthy subjects are equally responsive to the RNAdjuvant ® [34]. However, the immunological effect of adjuvants in cancer patients undergoing chemotherapy remains to be demonstrated.…”