Immunomodulatory Monoclonal Antibodies in Combined Immunotherapy Trials for Cutaneous Melanoma

Abstract

In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there is still a way on the road to achieving complete and long-lasting responses in most patients. It is desirable that immunotherapeutic strategies induce diverse immune reactivity specific to tumor antigens, including the so-called neoantigens, as well as the blockade of immunosuppressive mechanisms. In this review, we will go through the role of promising monoclonal antibodies in cancer immunotherapy with immunomodulatory function, especially blocking of the inhibitory immune checkpoints CTLA-4 and PD-1, in combination with different immunotherapeutic strategies such as vaccines. We will discuss the rational basis for these combinatorial approaches as well as different schemes currently under study for cutaneous melanoma in the clinical trials arena. In this way, the combination of "push and release" immunomodulatory therapies can contribute to achieving a more robust and durable antitumor immune response in patients.

Keywords: clinical trials; combined tumor immunotherapy; cutaneous melanoma; immune checkpoint blockade; monoclonal antibodies.

Figure 1

Immunomodulatory monoclonal antibodies and combination strategies in cutaneous melanoma immunotherapy. Different immunotherapeutic strategies are currently being assessed in combination in clinical trials that either “push” tumor immunoreactivity or “release” from inhibitory immune-regulatory mechanisms, fostering this way an antitumor immune response.