Gaining ground on a cure through synergy: combining checkpoint inhibitors with cancer vaccines

Abstract

The approval of multiple checkpoint inhibitors (CPIs) for the treatment of advanced malignancies has sparked an explosion of research in the field of cancer immunotherapy. Despite the success of these medications, a large number of patients with advanced malignancy do not benefit from therapy. Early research indicates that a therapeutic combination of cancer vaccines with checkpoint inhibitors may lead to synergistic effects and higher response rates than monotherapy. Areas covered: This paper summarizes the previously completed and ongoing research on this exciting combination, including the use of the tumor lysate, particle-loaded dendritic cell (TLPLDC) vaccine combined with checkpoint inhibitors in advanced melanoma. Expert commentary: Increasing experience with CPIs has led to improved understanding of which patients may benefit and it is increasingly clear that the presence of a pre-existing immune response to the tumor, along with tumor-infiltrating lymphocytes, is key to the success of CPIs. One exciting possibility for the future is the addition of a cancer vaccine to CPI therapy, eliciting these crucial T cells, which can then be augmented and protected by the CPI. A number of current and future studies are addressing this very exciting combination therapy.

Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses

“…DCV is worthy of further study combined or sequenced with these other agents. Other dendritic cell vaccines and patient-specific vaccine approaches already are showing promise in combination with checkpoint inhibitors [ 37 , 38 ].…”

A framework for the development of effective anti-metastatic agents

“…A framework for the development of effective anti-metastatic agents Robin L. Anderson 1,2,3 , Theo Balasas 4 , Juliana Callaghan 5 , R. Charles Coombes 6 , Jeff Evans 7 , Jacqueline A. Hall 8 , Sally Kinrade 3,9 , David Jones 10 , Paul S. Jones 11 , Rob Jones 7 , John F. Marshall 12 , Maria Beatrice Panico 10 , Jacqui A. Shaw 13 , Patricia S. Steeg 14 , Mark Sullivan 3,9 , Warwick Tong 3 , Andrew D. Westwell 15 and James W. A. Ritchie 4,11…”

“…Metastasis of cancer to distal sites is associated with poor patient prognosis and is the foremost cause of cancer-related death 1 , with approximately 90% of patients who succumb to cancer dying of metastatic disease 2 . Despite the advent of effective immuno therapies within the past decade, the majority of patients with advanced-stage and/or high-risk cancers continue to die as a direct result of metastatic disease or owing to complications of its treatment 3 . Indeed, improvements in the survival of patients with cancer over time have not equally benefited those with metastatic disease 4 .…”

Vaccinations for Anal Squamous Cancer: Current and Emerging Therapies

“…Both CTL and regulatory T-cell populations are stimulated in response to peptide antigens, but with CPIs, the opportunity to limit the impact of regulatory T-cells now exists. A combined, synergistic multi-immunotherapy treatment is being proposed for other malignancies 56,57 and should be further explored in anal cancer.…”