Immunogenic therapy in squamous celllung cancer

Background: Over a hundred years after the first description ofthis disease, lung cancer represents one of the major challengesin oncology. Radical treatment cannot be introduced in morethan ۷۰% of cases and overall survival rate does not exceed۱۵%.Very low and heterogonous antigenicity of lung cancer cellsleads to passive escape from anti-cancer immune defense. Thecytotoxic lymphocytes (CTLs) that play a main role in the anticancerresponse are actively suppressed in the tumor environmentand following regulatory mechanisms inhibit the recognitionof tumor antigens by antigen presenting cells.Materials and Methods: Therapeutic cancer vaccination isan antigen-specific immunotherapy that primes the immunesystem to produce antigen-specific antibodies, CD۴+ T helpercells and CD۸+ cytotoxic T-lymphocytes against relevanttumor-associated antigens. Recent favorable results of newertrials of therapeutic vaccines and checkpoint inhibitors haveproven against the common belief that lung cancer is nonimmunogenic.In particular, the checkpoint inhibitors targetingcytotoxic T-lymphocyte-associated antigen ۴ (CTLA-۴) andthe programmed death-۱ (PD-۱) pathway have shown durableclinical responses with manageable toxicity.Results: cell therapy uses gene transfer technology to reprograma patient's own T cells to stably express CARs, therebycombining the specificity of an antibody with the potent cytotoxicand memory functions of a T cell. Given this clinicalefficacy, preclinical development of CAR T-cell therapy for anumber of cancer indications has been actively investigated,and the future of the CAR T-cell field is extensive and dynamic.Conclusion: Several approaches to increase the feasibility andsafety of CAR T cells are currently being explored, includinginvestigation into mechanisms regulating the persistence ofCAR T cells. Additionally, numerous early-phase clinical trialsare now investigating CAR T-cell therapy beyond targetingCD۱۹, especially in solid tumors