Therapeutic cancer vaccines: advancements, challenges and prospects

Abstract

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

“…Cancer vaccines amplify the signal of tumor-specific antigens (TSAs) or TAAs via encapsulated antigen-encoding DNA and RNA, peptides, or antigen-loaded APCs. 689 – 691 They actively stimulate patients’ own anti-tumor immune response at the very beginning of the cancer immunity cycle. With promising potential, 692 – 696 current research focuses on identifying antigens with the best quality and optimizing the delivery platform.…”

“…With promising potential, 692 – 696 current research focuses on identifying antigens with the best quality and optimizing the delivery platform. 689 – 691 High-throughput sequencing and bioinformatics tools in recent years have greatly facilitated the screening of highly immunogenic neoantigens. 692 , 697 Improved vectors 698 , 699 and immune adjuvants 700 – 702 have been reported to enhance the efficacy of vaccine delivery and the ensuing immune activation and tumor-killing effects in preclinical studies.…”

Layer-by-layer nanoparticle encapsulating all-trans retinoic acid and CpG as a mucosal adjuvant targeting colorectal cancer

“…8 Antigens are specific molecules or proteins utilized to train the immune system to selectively target cancer cells. 9 Adjuvants, on the other hand, function as immune stimulants, enhancing the immune response against tumor antigens. 10 The efficacy of cancer vaccines is determined by the selection of antigens and adjuvants.…”

Immunoinformatics Design and In Vivo Immunogenicity Evaluation of a Conserved CTL Multi-Epitope Vaccine Targeting HPV16 E5, E6, and E7 Proteins

“…Although current vaccines have demonstrated significant efficacy in preventing cervical cancer, they are unable to clear pre-existing HPV infections. Developing therapeutic HPV vaccines presents numerous challenges, including the rapid identification of viable target antigens, issues regarding cross-protection due to antigenic diversity and antigenic variation, im-mune evasion within the tumor microenvironment, as well as the assessment of vaccine immunogenicity and long-term safety [4,5].…”