XENOGENEIC ICAM-1 GENE-TRANSFER SUPPRESSES TUMORIGENICITY AND GENERATES PROTECTIVE ANTITUMOR IMMUNITY

Tumorigenicity in Fischer rats was not significantly reduced when the rat ICAM-1 gene was overexpressed in the rat tumor cell lines, JM-1 an d SST-2. When these rat tumor cell lines were genetically modified wit h a gene encoding human ICAM-1, tumorigenicity was dramatically reduce d. Expression of xenogeneic ICAM-1 did not alter the growth rate, expr ession of the major histocompatibility complex, nor morphological appe arance of the cells. However, it did facilitate a tumor-specific immun ological recognition and rejection of the genetically modified tumor c ells. This effect resulted in a tumor-specific, long-term protective i mmunity directed against genetically unmodified tumor cells. Most impo rtantly, administration of tumor cells genetically modified with genes encoding xenogeneic ICAM-1 can facilitate an immunological response t o genetically unaltered preexisting tumors. Transferring splenocytes f rom animals 'vaccinated' with the xenogeneic ICAM-1 gene altered tumor cells was able to transfer the antitumor response into recipient anim als. Furthermore, transfer of CD8(+) lymphocytes produced the same res ult. These results suggested that tumor specific CD8(+) T lymphocytes were activated by the xenogeneic altered tumor cells. This activation generated the long-term, tumor-specific immunity.