Abstract

Therapeutic cancer vaccines have proven to seldom induce dramatic clinical response when used alone, and therefore, they are being studied in combination with additional treatment modalities to achieve optimal treatment activities. Growing preclinical data show that combining vaccines and immune checkpoint inhibitors (ICIs) can prime intensified immunogenicity and modulate immunosuppressive tumor microenvironment. Herein, we focus on the safety and efficacy of approved and promising cancer vaccines alone or combined with ICIs in the treatment of several malignancies. Generally, the majority of clinical trials support the concept of synergy that combination therapy of vaccines and ICIs holds maximized potential to improve clinical outcomes. Importantly, the combination has acceptable safety and minimal additional toxicity compared with single-agent vaccines or ICIs. Additionally, the potential strategies of combining personalized tumor vaccines with ICIs will become priority option and future direction of vaccine development and application and the urgent need to develop effective biomarkers to screen appropriate patient populations and predict response to combination therapy.

Highlights

  • Cancer immunotherapy, including cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell therapy, represents a scientific breakthrough in the treatment of various malignancies (Kirkwood et al, 2012)

  • We focus on the safety and efficacy of approved and promising cancer vaccines alone or combined with ICIs for the treatment of several malignancies

  • The Food and Drug Administration (FDA) has approved two therapeutic cancer vaccines: sipuleucel-T for metastatic castration-resistant prostate cancer based on modest improvement in overall survival (OS), and T-VEC for unresectable advanced melanoma based on partial improvement in OS and durable response rate (DRR) (Kantoff et al, 2010a; Andtbacka et al, 2015)

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Summary

INTRODUCTION

Cancer immunotherapy, including cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell therapy, represents a scientific breakthrough in the treatment of various malignancies (Kirkwood et al, 2012). Combination Immunotherapy therapeutic cancer vaccines with additional treatment modalities has been explored, as an approach to augment immune responses and treatment activities. ICIs can enhance antitumor immune response by blocking these negative regulation signaling and have revolutionized the treatment landscapes of different tumor types such as melanoma, lung, renal cell, and bladder cancers (Hodi et al, 2010; Topalian et al, 2012). We highlight the enormous potential of personalized cancer vaccines in combination with ICIs, which can produce complete tumor regression in several studies, and hope to provide theoretical foundations and innovative ideas for the development and application of cancer vaccines in clinical settings

THERAPEUTIC CANCER VACCINES
Improved Immunosuppressive TME
RATIONALE FOR COMBINATION IMMUNOTHERAPY
Intensified Immunogenicity
CANCER VACCINES AND ICI COMBINATIONS
Ipilimumab Plus PROSTVAC
Ipilimumab Plus GVAX
Ipilimumab Plus Peptide Vaccine
Nivolumab Plus Peptide Vaccine
Emerging Progress in Combination Strategy
CHALLENGES AND FUTURE PERSPECTIVES
Optimization of Vaccine Platforms
Time Sequence and Clinical Settings
Findings
Biomarkers for Combination Therapy
Full Text
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