Historical review on thymosin alpha 1 in oncology: preclinical and clinical experiences

Thymosin a1 (Ta1) is a naturally occurring polypeptide that regulates immune cell development and function, and is also capable of interacting with multiple target cells with relevant biological effects. The rationale of Ta1 use in cancer treatment stems from the consideration that tumor progression is favored by a failure of the immune response and in turn induces immune suppression. This paper will review the historical background of Ta1 use in oncology, aiming to highlight the importance of Ta1 as an immunotherapeutic tool to be used in combination with chemotherapy, a concept that is not yet fully established in clinic. Areas covered: The efficacy and safety of combining Ta1 with chemotherapy and cytokines were first evaluated in murine tumor models, providing essential information about effects, mechanisms of action, doses and treatment protocols. The therapeutic potential of the chemo-immunotherapy protocol on metastatic melanoma and lung cancer has been confirmed in controlled clinical trials. Critical for the efficacy of the chemo-immunotherapy protocol is the dual action of Ta1 on immune effector and tumor cells. Expert opinion: On the basis of the preclinical and clinical results available, the use of the chemo-immunotherapy protocol, in which the role of Ta1 is central, is strongly recommended