Cancer vaccinesSection I: Clinical investigations in a specific cancer typeVaccines for Melanoma and Renal Cell Carcinoma
Section snippets
Tumor-Associated Antigens for Melanoma and Renal Cell Carcinoma
The basis for immune recognition of tumor cells is the presence of tumor-associated antigens. These antigens are proteins expressed by tumor cells, generally at higher expression levels, at altered points during cell differentiation or in mutated forms. This pattern of expression allows the immune system to detect abnormal cell characteristics, which can be used for targeting a malignant cell for immune-mediated destruction. Table 1 lists selected tumor-associated antigens that have been
Protein- and Peptide-Based Vaccine Approaches
The simplest strategy for vaccine development is to use whole proteins or peptide fragments of defined tumor-associated antigens. Although this approach is straightforward, most protein-/peptide-based vaccines lack significant immunogenicity and have not been able to induce a robust immune response when administered alone. For this reason, most clinical trials of peptide or protein vaccines have used immunologic adjuvants or other agents, such as cytokines or Toll-like receptor agonists,
Recombinant Vector-Based Vaccine Approaches
In contrast to peptide- and protein-based vaccine strategies, recombinant vectors provide a platform for the expression of one or more full-length gene segments. The simplest method is to use a DNA plasmid encoding the gene(s) of interest, although in vivo expression is often difficult to achieve. In contrast, genes can be engineered into viral vectors for vaccination or gene therapy approaches. This offers the advantage of easy manufacturing and delivery to patients and may provide additional
Whole Cell–Based Vaccine Approaches
Another strategy for vaccination is the use of whole cells as vaccines, which are typically irradiated prior to vaccination. Whole cell vaccines can be autologous, in which an individual patient's tumor is resected, irradiated, and prepared for immunization alone or admixes with an immunologic adjuvant. Alternatively, whole cell vaccines can be allogeneic based on a tumor cells or cell lines derived from other patients. Allogeneic whole cell vaccines have the advantage of not requiring
The Tumor Microenvironment and Immunological Escape
Despite the myriad of vaccine strategies that have been attempted in patients with melanoma and RCC, the vast majority of vaccine studies have resulted in disappointing results. This has led some to conclude that vaccination may not be a practical approach for treatment of these diseases.81 The encouraging therapeutic responses observed with nonspecific immunotherapeutic agents, such as IL-2 and ipilimumab, argue for further exploration of vaccines in the management of melanoma and RCC. Recent
Conclusions
The development of vaccine for melanoma and RCC has been a promising approach supported by considerable preclinical investigation and an improved understanding of the molecular and cellular basis of tumor cell recognition and destruction by the immune system. The success of nonspecific agents, such as high-dose IL-2 and anti-CTLA4 monoclonal antibody (ipilimumab), and the identification of tumor-associated antigens in melanoma and RCC tumor cells suggest that vaccination should be useful. A
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Amplifying antitumor T cell immunity with versatile drug delivery systems for personalized cancer immunotherapy
2022, Medicine in Drug DiscoveryCitation Excerpt :To facilitate the delivery of these antigens and promote the vaccination efficacy of autologous tumor sources, various drug delivery systems including nanoparticles and hydrogels have been designed to deliver ATVs locally or systemically for generating protective immunity, breaking immune resistance and inducing durable tumor-specific immunity [53,58-64]. The absence of co-stimulatory molecules and presence of immunosuppressive signals in tumor microenvironment have significantly weakened the immunization effect of ATVs [65]. To overcome these issues for extending the clinical application of ATVs, David J. Mooney and co-workers fabricated a whole tumor cell vaccine platform that co-loads liver tumor cells and adjuvants in a cryogel structure for inducing a potent and long-lasting immune response against tumor cells [64].
Adenovirus-mediated NDRG2 inhibits the proliferation of human renal cell carcinoma cell line OS-RC-2 in vitro
2014, Asian Pacific Journal of Tropical MedicineSystemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems
2013, International Journal of PharmaceuticsCitation Excerpt :To elicit potent immune response a DNA vaccine must be delivered and transported across cell membrane of the antigen presenting cells (APCs) in sufficient concentration while protected from nuclease mediated destruction (Allison and Byars, 1991). Polar and anionic nature of a plasmid DNA molecule does not readily allow transfer across the biological membranes (Kaufman, 2012). Therefore, one of the major challenges in DNA vaccination is optimal gene delivery to target immune cells.
Peptide therapeutics in the management of metastatic cancers
2022, RSC AdvancesThree-dimensional cryogels for biomedical applications
2019, Journal of Biomedical Materials Research - Part A
Conflict of interest: none.