Melanoma vaccines: developments over the past 10 years

Abstract

Decades of preclinical evaluation and clinical trials into melanoma vaccines have yielded spectacular progress in our understanding of melanoma antigens and the immune mechanisms of tumor rejection. Key insights and the results of their clinical evaluation are reviewed in this article. Unfortunately, durable clinical benefit following vaccination remains uncommon. Two recent clinical advances that will impact on melanoma vaccine development are trials with inhibitors of CTLA-4 and oncogenic BRAF. Long-term therapeutic control of melanoma will require integration of specific active immunotherapy with these emerging successful therapies from the disparate fields of immune regulation and signal transduction.

Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab

“…1 This typically requires specific T-cell clones recognizing tumor cellassociated peptide Ags in the context of MHC class I molecules. Multiple vaccination strategies, [2][3][4] anti-CTLA4 Abs boosting T-cell responses, 5,6 and adoptive transfer of ex vivo-expanded, tumorinfiltrating lymphocytes [7][8][9] have in many cases demonstrated the ability of tumor-specific T cells to treat late-stage cancers, albeit often with low response rates. Likewise, numerous mouse models have shown eradication of solid tumors by cytotoxic T-cell responses and long-term protection from recurrence.…”

HLA-A*0201 + Plasmacytoid Dendritic Cells Provide a Cell-Based Immunotherapy for Melanoma Patients

“…In addition, it does not prevent tumor relapse or resistance (Nazarian et al, 2010). Thus, there is still an unmet need for new strategies able to widely and efficiently cure melanoma with minimal side effects (Klein et al, 2011).…”

NK Cells Are Required for Dendritic Cell–Based Immunotherapy at the Time of Tumor Challenge

“…Current treatment options include surgery in combination with chemotherapy, postoperative radiation therapy, adjuvant therapy with IFN-a-2b, or targeting intracellular pathways such as BRAF (2)(3)(4). As melanoma is an immunogenic tumor, vaccines have been investigated in the hope of enhancing antitumor responses through the improvement of Ag presentation to naive and memory T cells (4) or as restimulation protocols following infusion of ex vivo-expanded, tumor Ag-specific T cells (5). The range of vaccines developed have included cell lysates, peptide/protein-based vaccines, cytokine-based vaccines, and whole-tumor cell vaccines with a wide variety of delivery systems, adjuvants, injection frequencies, and routes of administration being investigated (6).…”

“…To date, vaccines that have been trialed have been derived from melanoma-associated tumor Ags including gp-100, MART-1, TRP-2, and GD3-ganglioside. With the possible exception of available adoptive T cell therapy, vaccines have not yielded a significant improvement in overall survival in patients with resected melanoma above that of standard chemotherapy (2)(3)(4)(5)(6)(7).…”