K. Wei et al., XENOGENEIC ICAM-1 GENE-TRANSFER SUPPRESSES TUMORIGENICITY AND GENERATES PROTECTIVE ANTITUMOR IMMUNITY, Gene therapy, 3(6), 1996, pp. 531-541
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.