Abstract

Cancer vaccines based on tumor cell components have shown promising results in animal and clinical studies. The vaccine system contains abundant tumor antigen components, which can activate the immune system by antigens. However, their efficacy has been limited by the inability of antigens delivery, which are the core components of vaccines, further fail to be presented and activation of effective cells. Nanotechnology offers a novel platform to enhance the immunogenicity of tumor-associated antigens and deliver them to antigen-presenting cells (APCs) more efficiently. In addition, nanotreatment of tumor cells derivate active ingredients could also help improve the effectiveness of cancer vaccines. In this review, we summarize recent advances in the development of cancer vaccines by the combination of nanotechnology and tumor-based ingredients, including liposomes, polymeric nanoparticles, metallic nanoparticles, virus-like particles and tumor cells membrane, tumor lysate, and specific tumor antigens. These nanovaccines have been designed to increase antigen uptake, prolong antigen presentation, and modulate immune responses through codelivery of immunostimulatory agents. We also further discuss challenges and opportunities in the clinical translation of these nanovaccines.

Introduction

Cancer immunotherapy has revolutionized cancer treatment by harnessing the immune system to recognize and attack cancer cells [1–۳]. Among various immunotherapeutic approaches, cancer vaccines have attracted significant attention due to their potential to induce long-lasting and specific immune responses against tumor cells [4–۷]. By comparison with surgery, it hardly produce large wounds, nor does it cause higher toxicity in normal tissues and drug tolerance like chemotherapy in the treatment of tumor. However, the clinical efficacy of cancer vaccines based on tumor cell components, such as peptides and proteins, is limited by their poor immunogenicity and inefficient delivery to antigen presentation cells (APCs). Although, many cancer vaccines were applied with the immune-stimulatory agents, such as the programmed cell death protein 1 (PD-1), CpG oligonucleotide, etc. The clinical response rates remain low, especially in the hypoimmunogenic tumors. As we all know, pancreatic cancer is a more difficult type for immunotherapy as a low immunogenic tumor. Therefore, there are few effective cancer vaccines that can actively promote the pancreatic cancer treatment. Meanwhile, limited by the specific tumor antigens, the development of cancer vaccines was extremely difficult.

The field of cancer vaccines has seen significant advancements in recent years, with numerous studies focusing on different aspects of vaccine development and application [8–۱۲]. These advances have been facilitated by the exploration of various types of cancer vaccines, including those targeting viral antigens, neoantigens, and other tumor-specific antigens [13–۱۶]. One approach in cancer vaccine research involves targeting shared antigens from viral infections linked to certain cancer types, such as Epstein–Barr virus and HPV. Studies have shown promising results with vaccines targeting viral antigens like Epstein–Barr nuclear antigen 1 and latent membrane proteins, as well as HPV-related antigens, demonstrating favorable antitumor efficacy and the potential to establish durable T cell memory in rapidly progressing HPV-positive tumors [17]. Another significant area of research is neoantigen cancer vaccines. Neoantigens, derived from nonsynonymous cell variants, are only expressed in tumor cells and can bypass thymus-negative selection, leading to robust neoantigen-specific T cell responses [14]. Advances in genomic and transcriptional profiling have made identifying putative neoantigens possible, although challenges remain in predicting which neoantigens can effectively induce neoantigen-specific T cell responses [18–۲۰]. Cancer vaccines are being developed to stimulate antitumor immunity with tumor antigens delivered in various forms, such as cells, peptides, viruses, and nucleic acids [21–۲۴]. These vaccines aim to overcome tumor heterogeneity and reverse the immunosuppressive microenvironment. Challenges in the field include single antigen targeting, weak immunogenicity, off-target effects, and impaired immune response [25–۲۷]. Current research and reviews provide insights into the principle of action, components, classification, delivery methods, and progress of cancer vaccines, offering a broader perspective for future vaccine design.

Recent studies have shown that tumor antigens can be used for the design of cancer vaccines without the necessity to identify, parse, and reconstruct certain antigens [28–۳۱]. A novel concept has been proposed that the whole antigen vaccine systems derived from tumor cells could be designed to conquer cancer treatments [32–۳۴]. The tumor cells themselves are a huge antigen pool with countless tumor antigen epitopes, which can be used to activate antitumor immune response. Among them, more studies have focused on the application of tumor cell membrane as tumor antigens to stimulate APCs and further activate the antitumor immune response of T cells. In addition, the activation of T cells in immune response requires the involvement of costimulatory molecules. Some studies are based on this theoretical foundation, using genetic engineering to modify tumor cell membranes. By retaining antigen on the cell membrane and inducing the expression of costimulatory molecule CD80, T cells can be directly activated, thereby achieving antitumor immune response [35] (Figure 1). Of course, many studies combine tumor cell membranes that retain tumor antigens with other functional molecules to directly activate dendritic cells (DCs) for antigen presentation, leading to the activation of T cell immune response. These are two different approaches aimed at achieving the same goal [36–۳۸]. A series of nanovaccines developed on this basis have been widely used in the treatment of different tumor cells and preclinical experiments.