Tumor antigen

Tumble test Tumbling Tumeric Tumor antigens Tumor cells Tumor imaging Tumor necrosis Tumor necrosis factor... 

The active immunotherapeutic approach is specific and based on the premise that tumor antigens are immunogenic and the host is sufficientiy immunocompetent to mount an effective immune response to an autologous tumor. Theoretically, a weak or suppressed host immune system that had allowed the formation of a tumor may be overridden by active immunization or immunostimulation. In practice, vaccines composed of so-called autologous tumor extracts have been used to treat patients with malignant melanoma (73), and purified melanoma tumor-associated antigens have been used to ehcit antibody responses in melanoma patients (74). 

NHS-LC-biotin can be used to add a biotin tag to monoclonal antibodies directed at certain tumor antigens. The biotinylated monoclonals are allowed to bind to the tumor cell surfaces in vivo, and subsequent administration of an avidin or streptavidin conjugate can form the basis for inducing cytotoxic effects or creating traceable complexes for use in imaging techniques (Hnatowich et al., 1987). 

Antibody component directed against tumor antigen... 

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

Brichory, F., et al., "Proteomics-Based Identification of Protein Gene Product 9.5 as a Tumor Antigen that Induces a Humoral Immune Response in Lung Cancer," Cancer Res., 61, 7908-7912 (2001). 

Wikenheiser KA, Vorbroker DK, Rice WR, Clark JC, Bachurski CJ, Oie HK, Whitsett JA (1993) Production of immortalized distal respiratory epithelial cell lines from surfactant protein C/simian virus 40 large tumor antigen transgenic mice. Proc Natl Acad Sci USA 90(23) 11029-11033... 

Bartek, J., J. Bartkova, N. Kyprianou, E. N. Lalani, Z. Staskova, M. Shearer, S. Chang, and J. Taylor-Papadimitriou. 1991. Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian vims 40 large tumor antigen with a recombinant retrovirus. Proc Natl Acad Sci USA 88(9) 3520-4. 

Maltzman, W. and h. Czyzyk, UV irradiation stimulates levels of p53 cellular tumor antigen in nontrans-formed mouse cells. Mol Cell Biol,... 

Since the concept of professional suppressor cells is recovering interest among the immunological community, it is now time to consider how the manipulation of regulatory/suppressor T cells might be used clinically. As tumor antigens are an... 

Novellino L, Castelli C, Parmiani G. A listing of human tumor antigens recognized by T cells March 2004 update. Cancer Immunol Immunother 2005 54 187. 

Tumor cells in the first metastasis escaped immune recognition due to selective loss of HLA haplotype, but maintain the expression of HLA-A2 antigen. In contrast, in the second metastasis immune escape from immune dominant antigen-specific T cell responses were mediated by HLA class I downregulation which results in the impaired presentation of this epitope, whereas another tumor antigen-specific epitope was presented. This resulted in the shift of the dominant T cell response to a subdominant targeted response. 

It is noteworthy that MHC class I downregulation is not the only escape mechanism available for tumors to avoid T cell responses other mechanisms such as downregulation of the tumor antigens, alterations of the apoptosis program, expression of inhibitory molecules, lack of expression of costimulatory molecules leading to immunological tolerance have been also described. The identification of defined immune escape mechanisms in human or mouse tumors point to the existence of active immunosurveillance which is important for the implementation T cell-based immunotherapy protocols. This information will further help to select patients suitable for such therapies. Furthermore, restoration of the tumor MHC class I phenotype to a normal MHC phenotype may be an other strategy to restore an efficient immune response in cancer patients. All these approaches are still hypothetical and no clinical procedures have been tested so far. 

Transformed cells expressing tumour-specific surface antigens, which closely resemble normal surface antigens, may not induce an immune response. Furthermore, some tumor antigens, while not usually expressed in adults, were expressed previously during the neonatal period (i.e. just after birth) and are thus believed by the immune cells to be self. 

In contrast to the above situation, cancers induced by viruses generally exhibit immunological cross-reactivity. Any specific virus will often induce expression of the same tumour antigen, no matter what cell type it transforms. Moreover, in some cases, different transforming viruses can induce production of the same tumor antigen(s). Immunodetection/immunotherapy of such cancers is thus rendered attractive. Once a tumour antigen is identified, antibodies raised against it will likely cross-react with several other tumour types. 

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

Le Naour F, Misek DE, Krause MC, et al. (2001) Proteomics-based identification of RS/ DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res 7, 3328-35. 

Brichory F, Beer D, Le Naour F, Giordano T, Hanash S. (2001) Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer. Cancer Res 61, 7908-12. 

Prasannan L, Misek DE, Hinderer R, Michon J, Geiger JD, Hanash SM. (2000) Identification of beta-tubulin isoforms as tumor antigens in neuroblastoma. Clin Cancer Res 6, 3949-56. 

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