Historical review on thymosin α1 in oncology: preclinical and clinical experiences

Introduction: Thymosin alpha 1 (T alpha 1) 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 T alpha 1 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 T alpha 1 use in oncology, aiming to highlight the importance of T alpha 1 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 T alpha 1 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 T alpha 1 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 T alpha 1 is central, is strongly recommended.