Therapeutic Cancer Vaccines—Antigen Discovery and Adjuvant Delivery Platforms

Abstract

For decades, vaccines have played a significant role in protecting public and personal health against infectious diseases and proved their great potential in battling cancers as well. This review focused on the current progress of therapeutic subunit vaccines for cancer immunotherapy. Antigens and adjuvants are key components of vaccine formulations. We summarized several classes of tumor antigens and bioinformatic approaches of identification of tumor neoantigens. Pattern recognition receptor (PRR)-targeting adjuvants and their targeted delivery platforms have been extensively discussed. In addition, we emphasized the interplay between multiple adjuvants and their combined delivery for cancer immunotherapy.

A Brief Overview of Cancer Vaccines

“…Tumor-associated antigens are exemplified by oncofetal antigens, which are expressed only during fetal development and in malignant tissue but not other normal tissues of the body. Tumor-derived antigen selection and delivery are a major present focus of tumor immunology, with the most recent trend being to use next-generation sequencing technology to develop personalized, neoantigen-based vaccine therapies 1,3,8,9 . Because neoantigens are unique to cancer cells, unlike tumor-associated antigen, they are not expected to be subject to thymic selection and central tolerance and should therefore be capable of eliciting high-avidity T cells.…”

“…Accordingly, adjuvants have received a great deal of attention from cancer vaccinologists, but without the breakthrough results produced for infectious disease vaccines. Pathogens, particulates, saponins, and emulsions such as incomplete Freund's adjuvant (e.g., Montanide) have all been explored extensively, especially in peptide and recombinant virus vaccine preparations, and considerable work continues to be devoted to the question of an effective adjuvant(s) for cancer vaccines 9,14 . Recently, nanoparticle-based adjuvants have generated some interest, including antigen-delivery substances that may be “auto-adjuvanting.” 15 …”

“…Tumor-derived antigen selection and delivery are a major present focus of tumor immunology, with the most recent trend being to use next-generation sequencing technology to develop personalized, neoantigen-based vaccine therapies. 1,3,8,9 Because neoantigens are unique to cancer cells, unlike tumor-associated antigen, they are not expected to be subject to thymic selection and central tolerance and should therefore be capable of eliciting high-avidity T cells. However, challenges remain in developing neoepitope prediction algorithms that reliably identify candidates that will trigger genuine antitumor immune responses.…”

“…Pathogens, particulates, saponins, and emulsions such as incomplete Freund's adjuvant (e.g., Montanide) have all been explored extensively, especially in peptide and recombinant virus vaccine preparations, and considerable work continues to be devoted to the question of an effective adjuvant(s) for cancer vaccines. 9,14 Recently, nanoparticle-based adjuvants have generated some interest, including antigen-delivery substances that may be "auto-adjuvanting." 15 Because most cancer vaccines have sought to recruit T cell immunity, there also has been much effort dedicated to defining mechanisms of T cell help most relevant to antitumor immune responses.…”

A novel fluoropolymer as a protein delivery vector with robust adjuvant effect for cancer immunotherapy

“…In recent years, nanovaccine-based immunotherapy has emerged as a highly promising therapeutic approach in the field of cancer treatment. [1][2][3] During the immunotherapy process, the tumor-relative antigens are first captured by antigenpresenting cells (APCs, e.g., dendritic cells/DCs) and presented to T cells via the major histocompatibility complex (MHC) pathway, inducing the activation of CD4 + and CD8 + T cells. Then, the active T cells can infiltrate into the tumor tissues and eliminate the tumor cells by the effector cytokine and cytotoxic T cells.…”