Application of Nanotechnology in Therapeutic Cancer Vaccines

Abstract

Cancer can significantly lower the quality of life of human beings. Numerous treatments have thus far been developed to treat cancer, namely, surgery, radiotherapy, and chemotherapy. [1] Cancer treated with surgery has a high chance of recurrence because the boundary between the malignant tumor and the surrounding tissues and organs is indistinct. This problem also increases the probability of lymphatic and hematogenous metastasis. [2] Radiotherapy and chemotherapy eliminate not only tumor cells but also normal cells, causing harm to patients. Cancer can trigger tumor-specific immune responses, which has spurred the development of cancer vaccines. [3] Cancer vaccines can induce tumor regression or prevent tumor formation while establishing an enduring antitumor memory effect. [4] 1.1. Basic Concepts Cancer vaccines typically include tumor antigens, adjuvants, and delivery vehicles. The effectiveness of cancer vaccines primarily relies on three critical steps (Figure 1): 1) antigen uptake by antigenpresenting cells (APCs); 2) presentation of antigens to T cells by APC, followed by T cell activation; and 3) elimination of tumors by effector T cells. [5] Poor stability of antigens, immune escape, and low immunogenicity hinder the development of cancer vaccines. [6] Adjuvants that can improve the adaptive immune response of the body to antigens have been developed in response to the weak immunogenicity of cancer vaccines. [7] They enhance immune responses to tumor antigens, [8] as well as effectively avoid the immune suppression produced by the body, [9] thereby improving the immunotherapy efficiency of cancer vaccines. Aluminum salt adjuvants, pattern recognition receptor agonists, and polypeptides, among others, exhibit good immune activation. [10] Polymeric nanoparticles provide a promising platform for delivering adjuvants that can enhance antigen uptake by adjusting physical and chemical properties, including shape, size, electrical properties, polarity, processing, and presentation. [11] In addition, nanoadjuvants can enhance the stability of antigens and influence the release kinetics of cancer vaccines. [12] Tumor antigens can be classified as tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs). [13] TAAs are more highly expressed in tumor cells than in normal tissues but lack complete specificity for tumors. In contrast, TSAs are abnormal proteins produced by cancer cells via nonsynonymous mutations. [14] TSAs are expressed on tumor cells and are relatively highly immunogenic. [15] The high safety and the reduced off-target side effects render TSAs ideal as targets for tumor immunotherapy. [16] With the rapid development of genomics and bioinformatics, the screening and identification of TSAs are more accurate and faster. Cancer therapeutic vaccines based on TSAs have demonstrated clinical efficacy and exhibited good application prospects. [17] History and Current SituationThe history of tumor antigens and cancer vaccines is summarized in Figure 2. William Coley discovered a mixed bacterial

Recent Advances in Cancer Immunotherapy with a Focus on FDA-Approved Vaccines and Neoantigen-Based Vaccines

“…As vaccines are generated under good manufacturing practices and in large quantities, scaling up the production of small nucleic acids and associated delivery technology remains a challenge [1]. The cold-chain requirements necessary to prevent nucleic acid degradation also pose a challenge [4]. While a peptide vaccine would likely be the most cost effective option, an mRNA vaccine would be the most time efficient.…”

“…The simplicity, safety, low cost, and extensive studies are all major advantages [26]. The most significant disadvantages are the low immunogenicity, easy degradation, short half life, and potential for the tumor cell to evade detection via mutation [4]. The issue with immunogenicity can be overcome through the addition of an adjuvant to improve the immune response, prevent degradation, and lengthen the half life.…”

“…To briefly describe the origin and major advancements of cancer immunotherapy, it began with William Coley's application of an inactivated bacterial toxin in osteosarcoma. Coley published results in 1893 [4] showing some tumor regression [2] and encouraged further research to prove that vaccines can induce an immune response resulting in tumor clearance. Then, in the early 1900s, Paul Ehlrich's work regarding the immune surveillance hypothesis laid the foundation for modern immunotherapy [2].…”

The future of cancer immunotherapy: DNA vaccines leading the way

“…One such example of Th peptide is pan DR epitope (PADRE), which indeed increased the anti-tumor effects of the immune system [ 18 , 55 ]. A number of clinical trials are in the ongoing phase to evaluate the efficacy of polyepitope DNA vaccines for breast, cervical, ovarian, and pancreatic cancers [ 36 , 56 – 60 ].The illustration depicting the Types of DNA constructs has been depicted in Fig. 1 .…”