MHC class I+ and class I- HPV16-associated tumours expressing the E7 oncoprotein do not cross-react in immunization/challenge experiments.
It has been demonstrated repeatedly that a high proportion of tumours derived from MHC class I+ precursors are MHC class I-. Since a major task in immunotherapy strategies for treatment of malignancies is to develop polyvalent tumour vaccines efficient against a broad spectrum of tumours, we have examined whether MHC class I+ cell-based tumour vaccines can cross-protect against homologous MHC class I- tumour challenge and vice versa. For these purposes, we have used two oncogenic cell lines induced independently by co-transfection of murine H-2b cells with E61E7 HPV16 and activated Ha-ras oncogenes, the tumours TC-1 (MHC class I+, HPV16 E7+) and E7+). Surprisingly, it was found that these two tumours do not cross-react, although both of them contain the crucial HPV16-coded tumour rejection antigen E7. Preimmunization with the MHC class I+ tumour did not protect against a subsequent challenge with the MHC class I- tumour and vice versa; however, immunization with the TC-1 tumour could protect syngeneic mice against the TC-1 tumour challenge and, similarly, immunization with the MK16/1/IIIABC tumour could protect mice against the MK16/1/IIIABC tumour challenge. If this finding can also be confirmed as a more general phenomenon with other MHC class I+ and class 1- tumours, it could have serious implications for design of immunotherapeutic vaccines and protocols.
Símová
J
J
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Mikysková
R
R
Vonka
V
V
Bieblová
J
J
Bubeník
J
J
Jandlová
T
T
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D003429:Cross Reactions; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D027383:Papillomaviridae / Q000235:genetics* / Q000276:immunology; D030361:Papillomavirus Infections / Q000276:immunology*
D015395:Histocompatibility Antigens Class I