Immunostimulants in Cancer Therapy

Abstract

During the past few decades, immunotherapy has become a clinical reality, and an ever-increasing number of cancer patients are receiving immunologic intervention(s). The therapeutic focus has been on the development of interventions that initiate or boost an existing immune response against a patient’s tumor. Indeed, in 2013, the clinical success of immunotherapy was recognized by the editors of Science Magazine with the designation of “Breakthrough of the Year” [1]. Nonetheless, we have only just begun to understand and develop the potential of immunotherapy. Ongoing clinical studies are testing the safety and efficacy of biologic, molecular, and cellular therapeutic regimens either as stand-alone interventions or in combination with standard of care therapy. Immunoaugmenting drugs have been used to treat disease since early in the twentieth century when William B. Coley treated cancer patients with mixed bacterial toxins [2]. These studies stimulated the clinical use of microbial substances, such as Bacillus Calmette-Guérin (BCG) (bladder cancer, United States), Krestin, Picibanil and lentinan (gastric and other cancers, Japan), and Biostim and Broncho-Vaxom (recurrent infections, Europe). While these unsophisticated drugs can induce various immunopharmacological activities, their use is associated with regulatory obstacles due to impurity, lot-to-lot variability, unreliability, and adverse side effects. Similarly, traditional herbal medicines (Asia) can act as a source of active substances for immunotherapy but require purification, characterization, and synthetic production of the active moieties. Purified entities derived from natural products that are in “routine” clinical use includes Bestatin®, Taxol®, FK-506, rapamycin, deoxyspergualin, and cyclosporine, all of which are derived from natural products. The current immunotherapy focus is on the use of monoclonal antibodies such as checkpoint inhibitors and recombinant proteins (cytokines), although the utility of these drugs can be limited due to immunotoxicity and pharmacological deficiencies. However, there remains a potential utility for biological response modifiers (BRM) due to their ability to induce multiple cytokines for immune augmentation and hematopoietic restoration.