Methods for improving the immunogenicity and efficacy of cancer vaccines

ABSTRACT

Introduction: Cancer vaccines represent one of the oldest immunotherapy strategies. A variety of tumor-associated antigens have been exploited to investigate their immunogenicity as well as multiple strategies for vaccine administration. These efforts have led to the development of several clinical trials in tumors with different histological origins to test the clinical efficacy of cancer vaccines. However, suboptimal clinical results have been reported mainly due to the lack of optimized strategies to induce strong and sustained systemic tumor antigen-specific immune responses.

Areas covered: We provide an overview of different types of cancer vaccines that have been developed and used in the context of clinical studies. Moreover, we review different preclinical and clinical strategies pursued to enhance the immunogenicity, stability, and targeting at tumor site of cancer vaccines.

Expert opinion: Additional and appropriate preclinical studies are warranted to optimize the immunogenicity and delivery of cancer vaccines. The appropriate choice of target antigens is challenging; however, the exploitation of neoantigens generated from somatic mutations of tumor cells represents a promising approach to target highly immunogenic tumor-specific antigens. Remarkably, the investigation of the combination of cancer vaccines with immunomodulating agents able to skew the tumor microenvironment from immunosuppressive to immunostimulating will dramatically improve their clinical efficacy.

KEYWORDS:

• Cancer vaccines
• tumor-associated antigens
• immunogenicity
• neoantigens
• immunomodulating agents
• combination studies

Article highlights

This review covers:

• The usage of peptide-, whole cell-, DNA/RNA-, virus-, heat shock protein-, and anti-idiotypic-based vaccinations highlighting advantages and limitations.

• The highly immunogenic role of neo-antigens, generated by tumor-associated somatic mutations, without toxic effect to normal tissues and their exploitation for cancer vaccines.

• The advantages and improvement of clinical responses through the combination of cancer vaccines with either immune checkpoint blockade or standard therapies.

• Strategies to improve and modulate the immunogenicity of tumor cells and TME through the usage of epigenetic drugs or immune checkpoint targeting agents.

• Hurdles in efficiency of delivery and administration of cancer vaccines and how the usage of biomaterials or targeting of immunizing agents at tumor site can improve the efficacy of vaccination.

• The achievement of a comprehensive molecular and immunogenic profiling of CICs/CSCs will allow to improve their targeting in order to gain the complete eradication of malignant lesions. This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

C Maccalli has received a grant from the Qatar National Research Fund (grant no. NPRP10-0129-170277). S Ferone has received sponsorship funding from DOD (grant no. W81XWH-16-1-0500) & NCI (grant no. RO1DE028172, RO3CA216114, RO3CA223886 and RO3 CA231766) .