Article

SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma.

Gene Therapy Center, and Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Cancer Gene Therapy (impact factor: 2.8). 04/2000; 7(3):446-55. DOI:10.1038/sj.cgt.7700124
Source: PubMed

ABSTRACT Evaluation of immunotherapy strategies in mouse models of carcinoma is hampered by the limited number of known murine tumor antigens (Ags). Although tumor Ags can be identified based on cytotoxic T-cell activation, this approach is not readily accomplished for many tumor types. We applied an alternative strategy based on a humoral immune response, SEREX, to the identification of tumor Ags in the murine colon adenocarcinoma cell line MC38. Immunization of syngeneic C57BL/6 mice with MC38 cells by three different methods induced a protective immune response with concomitant production of anti-MC38 antibodies. Immunoscreening of an MC38-derived expression library resulted in the identification of the endogenous ecotropic leukemia virus envelope (env) protein and the murine ATRX protein as candidate tumor Ags. Northern blot analysis demonstrated high levels of expression of the env transcript in MC38 cells and in several other murine tumor cell lines, whereas expression in normal colonic epithelium was absent. ATRX was found to be variably expressed in tumor cell lines and in normal tissue. Further analysis of the expressed env sequence indicated that it represents a nonmutated tumor Ag. Polynucleotide immunization with DNA encoding the env polypeptide resulted in strong and specific antibody responses to this self Ag in all immunized mice. Thus, SEREX offers a rapid means of identifying tumor Ags in murine cancer models.

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    Article: Current concepts in cancer vaccine strategies.
    B Monzavi-Karbassi, T Kieber-Emmons
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    ABSTRACT: Cancer vaccines are entering a new phase of popularity, in part because of the recognition of when a therapeutic vaccine is most effective and the identification of appropriate target antigens. New technologies, most notably gene transfection into dendritic cell and DNA vaccination approaches, have spurred further clinical evaluations. While many researchers consider humoral responses as not being viable for large tumors, these responses may play a role in regulating micrometastases (i.e., adjuvant setting). The recent approval of antibodies as therapeutics for cancer treatment has lent to the viability of this therapy concept. The success of carbohydrate-conjugate vaccines in bacterial systems has also renewed interest in developing such vaccines for cancer immunotherapy. Carbohydrates can be further converted into peptide/protein mimetics with several of these mimetics in clinical trials. These mimetic forms can be manipulated into DNA vaccine types that may be combined into DNA cassettes that contain CTL-associated epitopes to further define a novel strategy for future vaccine development.
    BioTechniques 02/2001; 30(1):170-2, 174, 176 passim. · 2.67 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

alternative strategy
 
candidate tumor Ags
 
cytotoxic T-cell activation
 
different methods induced
 
DNA encoding
 
immunized mice
 
immunotherapy strategies
 
MC38 cells
 
MC38-derived expression library
 
murine ATRX protein
 
murine cancer models
 
murine tumor antigens
 
murine tumor cell lines
 
nonmutated tumor Ag
 
Polynucleotide immunization
 
self Ag
 
specific antibody responses
 
syngeneic C57BL/6 mice
 
tumor cell lines
 
tumor types
 

T A Hampton