Therapeutic cancer vaccination against telomerase: clinical developments in melanoma

Abstract

Purpose of reviewCheckpoint inhibitors (CPIs) have revolutionized treatment outcomes for patients with malignant melanoma. Long-term follow-up shows that a substantial subset of patients who exhibit clinical responses achieve extended overall survival. Nevertheless, most patients do not achieve durable benefit from CPIs, and improvements are urgently needed. The clinical efficacy of CPIs depends on highly variable preexisting spontaneous T-cell immune responses. Cancer vaccines represent an independent treatment modality uniquely capable of expanding the repertoire of tumor-specific T cells in cancer patients and thus have the capacity to compensate for the variability in spontaneous T-cell responses. Vaccines are, therefore, considered attractive components in a CPI-combination strategy.Recent findingsHere we discuss recent results obtained through therapeutic vaccination against telomerase human telomerase reverse transcriptase (hTERT). Recent publications on translational research and clinical results from phase I trials indicate that vaccination against telomerase in combination with CPIs provides relevant immune responses, negligible added toxicity, and signals of clinical efficacy.ConclusionIn the near future, randomized data from clinical trials involving therapeutic cancer vaccines and checkpoint inhibitors will be available. Positive readout may spark broad development and allow cancer vaccines to find their place in the clinic as an important component in multiple future CPI combinations.

BRAFV600E Metastatic Melanoma Journey: A Perspective from a Patient and his Oncologist

“…Mohr: I do think that we are now on the verge of the next major leap in research. There is currently a study on the adjuvant treatment of malignant melanoma through vaccination therapy; indeed, vaccination treatment trials are ongoing in all stages of melanoma [36][37][38]. Importantly, the use of next-generation sequencing has given scientists the opportunity to design personalised vaccines that can target tumour-specific antigens (neoantigens) in individual melanoma tumours, with preliminary clinical evidence suggesting that this approach has promising antitumour activity and good safety and tolerability [39].…”