Vaccines cancer

The use of viral vectors may ultimately prove more effective, as a T-cell response appears to be central to the immunological destruction of cancer cells. 

---

First clinical human gene therapy trials with polyplexes were performed using cancer vaccines based on autologous patient tumor cells. These were modified ex vivo with interleukin-2 pDNA. To obtain high level transfection rates of patient s primary tumor cells, Tf-PLL/pDNA polyplexes linked with inactivated endosomolytic adenovirus particles were applied [221]. Polymer-based in vivo human gene transfer studies were performed with PEGylated PLL polyplexes, delivering CFTR pDNA to the airway epithelium of cystic fibrosis patients [222],... 

Stern, P. 2000. Cancer vaccines and immunotherapy. Cambridge University Press. Subramanian, G. (ed.). 2004. Antibodies. Kluwer. 

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

Tn antigen a-GalNAc Cancer vaccine Lectin (Vicia villosa) 22-25... 

Another cell therapy method includes the excision of cells from the body. These cells are then modified and returned to the host body. Provenge, a cancer vaccine using cell therapy, has completed Phase III trial and is being reviewed by the FDA. The technique for this therapy is given in Exhibit 4.17. 

Provenge is a cancer vaccine using cell therapy technique. Dendritic cells are removed from patients. These cells are treated with the prostate-specific antigen prostatic acid phosphatase (PAP), which is present in 95% of prostate cancer cases. The activated dendritic cells are returned to the patients and they stimulate the T cells to destroy cancer cells expressing the PAP, thus treating the tumor. 

Source Jones D. Cancer vaccines on the horizon, Namre Reviews Drug Discovery 6 333-334 (2007). 

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. 

Source Fox JL. Uncertainty surrounds cancer vaccine review at 7T>A,Nature Biotechnology 25 827-828 (2007). 

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. 

Finn OJ. Cancer vaccines between the idea and the reality. Nat Rev Immunol 2003 3 630. 

Mitchell MS. Cancer vaccines, a critical review— Part II. Curr Opin Investig Drugs 2002 3(1) 150-158. 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

Stern, P. (2000). Cancer Vaccines and Immunotherapy. Cambridge University Press, Cambridge. 

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

Rosenberg, S. (1997). Cancer vaccines based on the identification of genes encoding cancer regression antigens. Immunol. Today 18(4), 175-182. 

Ragupathi G, Coltart DM, Williams LJ, Koide J, Kagan E, Allen J, Harris C, Glunz PW, Livingston PO, Danishefsky SJ. On the power of chemical synthesis immunological evaluation of models for multiantigenic evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc Natl Acad Sci USA 2002 99 13699-13704. 

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. 

Lipids A are also used in therapeutic cancer vaccination to cure tumors. In this case, lipids A are used as adjuvants, e.g. administered simultaneously with tumor extracts or tumor antigens, to increase the immunogenicity of the vaccine or to inhibit the tumor-induced tolerance. 

---