Antigen loss variants of a murine renal cell carcinoma: implications for tumour vaccination

Vaccination with tumour cells genetically modified to support induction of an immune response by either production of cytokines or by expression of costimulatory molecules provides a promising therapeutic approach. We have evaluated the efficiency of tumour vaccination using RENCA cells, a weakly immunogenic renal cell carcinoma of the BALB/c strain, which were stably transfected either with MHC class II or with B7.1 or with both. Tumour growth after vaccination with MHC class II and/or B7.1 transfected RENCA cells was extremely variable, with close to 100% protection after vaccination with some clones and no effect of vaccination with others. To unravel the underlying mechanism, untransfected RENCA cells were cloned and individual clones were tested for their immunogenicity. It turned out that cloned RENCA cells varied considerably in immunogenicity. Some clones grew very rapidly, others grew slowly in syngeneic BALB/c mice. However, all clones displayed comparable growth rates in nude mice and no differences in the proliferation rate was observed in vitro. Vaccination with rapidly growing clones was ineffective and, importantly, this feature remained unaltered by vaccination with MHC II class and/or B7.1 transfected clones. Instead, 8 out of 10 mice rejected the parental line after immunisation with a pool of MHC class II and B7.1 transfected clones, whereas after vaccination with non-transfected RENCA cells only 1 out of 10 animals remained tumour free. Finally, it should be mentioned that by cloning RENCA cells, we obtained one highly immunogenic clone (P2), vaccination with which was protective in 100% of mice. However, vaccination with this clone led to an individual-specific response, i.e. neither uncloned RENCA cells nor any other clone were rejected after vaccination with P2. This indicated that during the cloning procedure a new strongly immunogenic entity must have arisen. Taken together our study supports that vaccination with MHC II and/or B7.1 transfected tumour cells induces an efficient immune response, but only if the tumour is weakly immunogenic. However, extreme care should be taken to maintain bulk culture conditions because i.e. tumour may contain antigen loss variants and ii. new immunogenic entities may arise during the cloning procedure. Genetic manipulation for vaccination with both, antigen loss variants and with clones expressing an individual specific antigen will be in vain. (orig.)SIGLEAvailable from TIB Hannover: DtF QN1(63,7) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman