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 and SST-2. When these rat tumor cell lines were genetically modified with a gene encoding human ICAM-1, tumorigenicity was dramatically reduced. Expression of xenogeneic ICAM-1 did not alter the growth rate, expression of the major histocompatibility complex, nor morphological appearance of the cells. However, it did facilitate a tumor-specific immunological recognition and rejection of the genetically modified tumor cells. This effect resulted in a tumor-specific, long-term protective immunity directed against genetically unmodified tumor cells. Most importantly, administration of tumor cells genetically modified with genes encoding xenogeneic ICAM-1 can facilitate an immunological response to genetically unaltered pre-existing tumors. Transferring splenocytes from animals 'vaccinated' with the xenogeneic ICAM-1 gene altered tumor cells was able to transfer the antitumor response into recipient animals. Furthermore, transfer of CD8+ T lymphocytes produced the same result. These results suggested that tumors specific CD8+ T lymphocytes were activated by the xenogeneic altered tumor cells. THis activation generated the long-term, tumor-specific immunity.
Wei
K
K
Department of Cell Biology, Wellcome Research Laboratories, Research Triangle Park, NC 27709, USA.
Wilson
J G
JG
Jurgensen
C H
CH
Iannone
M A
MA
Wolberg
G
G
Huber
B E
BE
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics*; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D013997:Time Factors; D014162:Transfection / Q000379:methods
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1