Cancer vaccine development

Wang, R. 1999. Human tumor antigens implications for cancer vaccine development. Journal of Molecular Medicine 77(9), 640-655. 

Wang, R. Rosenberg, S. (1999). Human tumor antigens for cancer vaccine development. Immun. Rev. 170, 85-100. 

Tabi Z, Man S. Challenges for cancer vaccine development. Adv Drug Deliv Rev 2006 58 902-915. 

In this chapter, the main approaches in present cancer vaccine development for the treatment of solid tumours, current research directions, and critical challenges are discussed and some ongoing phase III trials are listed. 

Iscomatrix Immunostimulatory complex of a purified saponin fraction, cholesterol and phospholipid, which under defined conditions form cage-like structures typically 40 nm in diameter. The principal advantage of this combination is the reduction of toxicity of saponin component. Iscomatrix particulate vaccines are likely to be phagocytosed by macophages and induce cytokines such as IL-12 and IFN-y. They have a significant potential in cancer vaccine development [79]. 

Attempts to reproduce and extend Dr. Coley s results have been mixed. For one thing, his patients required multiple treatments that took time to work. For another, radiation or chemotherapy weakens the immune system so that it doesn t respond the same to fever. However, his tantalizing results hold promise for cancer vaccine development and improved cancer treatment strategies. 

Vaccine development is hampered by the fact that recurrent disease is common. Thus, natural infection does not provide immunity and the best method to induce immunity artificially is not clear. The genome of these vimses is also able to cause transformation of normal cells, thus conferring on them one of the properties attributed to cancerous cells. Vaccine made from herpes vimses must, therefore, be carefully purified and screened to eliminate the possibihty of including any active genetic material. 

While the FDA is adopting a cautious approach to cancer vaccine, such as DCVax-Brain, the Swiss Institute of Public Health has conditionally allowed the use of this vaccine by patients. DCVax consists of a patient s dendritic cells that have been pulsed with antigens derived from a tumor cell lysate prepared from surgically resected glioblastoma (brain cancer) tissue. It was developed by a company in the United States but has not yet been approved by the FDA. 

As gene therapy and stem cell research progress, we can expect more regulatory requirements to be developed to ensure proper safeguards are implemented. Similarly, xenotransplantation and control of biopharmaceutical products will experience specihe regulatory controls as new advances are made. Exhibit 11.13 presents the FDA s current oversight on gene therapy and its cautious approach to cancer vaccine. 

Hanna, N., and K. Hariharan, Development and application of PROVAX adjuvant formulation for subunit cancer vaccines. Adv Drug Deliv Rev, 1998. 32(3) 187-97. 

It is expected that in the near future antigen-specific vaccines will be applied effectively to induce strong T cell immune responses in patients displaying less progressed stages of disease. A comprehensive discussion on the development of therapeutic cancer vaccines (molecular vaccines) has been presented by Moingeon (2001) and Monzavi-Karbassi and Kieber-Emmons (2001). 

The overexpression of HER-2 protein in cancer cells makes it an ideal target for vaccines and other targeting strategies. Vaccines optimized to induce maximum T cell immunity to HER-2 may lead to potent in vivo antitumor immunity. HER-2 protein has been evaluated as a potential target for the development of cancer vaccines because preexistent T cell and antibody responses to HER-2 have been described in breast cancer patients (Disis and Cheever, 1996). In other words, breast cancer patients have preexisting immunity to the HER-2 receptor in the form of elevated antibody titers and T cell immunity. Elevated anti-HER-2 T cell responses have been demonstrated in breast and ovarian cancer patients following immunization with peptides derived from the HER-2 protein (Disis et al., 1999). However, whether peptide-specific T cell responses can be translated to antitumor immunity has yet to be established. 

Chabicovsky M, Ryle P. Non-clinical development of cancer vaccines regulatory considerations, Regul Toxicol Pharmacol 2006 44 226-37. 

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