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

Citation
Ta. Hampton et al., SEREX analysis for tumor antigen identification in a mouse model of adenocarcinoma, CANC GENE T, 7(3), 2000, pp. 446-455
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER GENE THERAPY
ISSN journal
0929-1903 → ACNP
Volume
7
Issue
3
Year of publication
2000
Pages
446 - 455
Database
ISI
SICI code
0929-1903(200003)7:3<446:SAFTAI>2.0.ZU;2-0
Abstract
Evaluation of immunotherapy strategies in mouse models of carcinoma is hamp ered by the limited number of known murine tumor antigens (Ags). Although t umor Ags can be identified based on cytotoxic T-cell activation, this appro ach is not readily accomplished for many tumor types. We applied an alterna tive strategy based on a humoral immune response, SEREX, to the identificat ion of tumor Ags in the murine colon adenocarcinoma cell line MC38. Immuniz ation of syngeneic C57BL/6 mice with MC38 cells by three different methods induced a protective immune response with concomitant production of anti-MC 38 antibodies. Immunoscreening of an MC38-derived expression library result ed in the identification of the endogenous ecotropic leukemia virus envelop e (env) protein and the murine ATRX protein as candidate tumor Ags. Norther n blot analysis demonstrated high levels of expression of the env transcrip t in MC38 cells and in several other murine tumor cell lines, whereas expre ssion in normal colonic epithelium was absent. ATRX was found to be variabl y expressed in tumor cell lines and in normal tissue. Further analysis of t he expressed env sequence indicated that it represents a nonmutated tumor A g. Polynucleotide immunization with DNA encoding the env polypeptide result ed in strong and specific antibody responses to this self Ag in all immuniz ed mice. Thus, SEREX offers a rapid means of identifying tumor Ags in murin e cancer models.