Immunotherapy for Melanoma: Current Status and Perspectives

Abstract

Summary Immunotherapy is an important modality in the therapy of patients with malignant melanoma. As our knowledge about this disease continues to expand, so does the immunotherapeutic armamentarium. Nevertheless, successful preclinical models do not always translate into clinically meaningful results. The authors give a comprehensive analysis of most recent advances in the immune anti-melanoma therapy, including interleukins, interferons, other cytokines, adoptive immunotherapy, biochemotherapy, as well as the use of different vaccines. We also present the fundamental concepts behind various immune enhancement strategies, passive immunotherapy, as well as the use of immune adjuvants. This review brings into discussion the results of newer and older clinical trials, as well as potential limitations and drawbacks seen with the utilization of various immune therapies in malignant melanoma. Development of novel therapeutic approaches, along with optimization of existing therapies, continues to hold a great promise in the field of melanoma therapy research. Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma. The need to engineer better immune interactions and to boost positive feedback loops appear crucial for the future of melanoma therapy, which ultimately resides in our understanding of the complexity of immune responses in this disease.

Current status of primary malignant melanoma of the esophagus: clinical features, pathology, management and prognosis

“…Also for advanced melanoma patients, high-dose interferon alfa-2b was conducted for postoperative adjuvant therapy [41] or other trials using a novel approach or agent such as peptide vaccination [42], molecular target drug [43], anti-CTLA4 [44] and anti-PD1 antibodies [45], nab-paclitaxel and carboplatin [46], or tasisulam sodium [47] were conducted and showed some effect. These results show it is still controversial, and no standard systemic therapy has been proven to increase overall survival even for a malignant melanoma.…”

Immunotherapy for metastatic melanoma

“…Though repeated T-cell activation with antigen-loaded DCs does occur, most of these studies have demonstrated that expansion of specific immune responses to tumor-antigen is often ephemeral, seldom yielding durable responses [Banchereau et al, 2001;Rosenberg et al, 2005;Alexandrescu et al, 2010]. Some successes have been noted with peptide-or tumor lysate-pulsed DCs, rendering them capable of eliciting CTL response.…”

“…The objective of modulating DCs by vaccine is to elicit an immune response, activating cytotoxic T lymphocytes (CTLs), which will react with and eventually reduce, or hopefully even eradicate, the tumor. DCs can process peptides from various tumor antigens, present the antigens, and activate immune responses [Alexandrescu et al, 2010]. Several experimental regimens have used peptide antigens, autologous, and/or allogenic tumor lysates.…”

Increased survival time of a patient with metastatic malignant melanoma following immunotherapy: A case report and literature review

“…FDA-approved treatments for metastatic melanoma including IL-2, chemotherapy, ipilimumab, vemurafenib, nivolumab and so on, and the median survival time given these treatments is from 6-24 months (15,22,23). Although the survival time of metastatic melanoma patients has improved, novel regimens remain critical to increase it further.…”