Abstract
IFN-γ genes were introduced through retroviral vectors into the high metastatic, low H-2Kb class I expressor, and poorly immunogenic 3LL-D122 clone. Two types of IFN-γ infectants were isolated: IFN-γ high secretors (128 to 256 IU/ml) and IFN-γ non- or very low secretors (<2 IU/ml). Both manifested high expression of MHC class I Ag. IFN-γ secretors showed significant decrease in tumorigenicity and metastatic growth, whereas IFN-γ nonsecretors retain tumorigenicity and were more metastatic than parental D122 cells. However, both groups, when inoculated in an irradiated form, induced similar high levels of CTL and protected mice to the same degree against a subsequent graft of parental cells. This indicates that enhanced expression of MHC class I and related genes caused by IFN-γ is the major participant in CTL induction. Immunization of mice carrying an established tumor of parental D122 cells with IFN-γ infectants is capable of almost completely preventing lung metastasis. Immunotherapy of tumor-bearing hosts is more effective when IFN-γ secreting cells are used as immunogens, indicating that mechanisms, in addition to CTL, are stimulated by secreted IFN-γ. Moreover, immunization with IFN-γ high secretors of postoperative mice, carrying established micrometastases, almost completely cured these mice. Support for the participation of non-T cell effectors in the response to IFN-γ secretors derives from the reduced tumorigenicity of these cells in CD1 nude mice. These data provide a rationale for the use of IFN-γ gene- transferred tumor cells as a modality for cancer therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 1458-1470 |
| Number of pages | 13 |
| Journal | Journal of Immunology |
| Volume | 150 |
| Issue number | 4 |
| State | Published - Jan 1 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Antimetastatic vaccination of tumor-bearing mice with two types of IFN-γ gene-inserted tumor cells. / Porgador, A.; Bannerji, R.; Watanabe, Y.; Feldman, M.; Gilboa, Eli; Eisenbach, L.
In: Journal of Immunology, Vol. 150, No. 4, 01.01.1993, p. 1458-1470.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antimetastatic vaccination of tumor-bearing mice with two types of IFN-γ gene-inserted tumor cells
AU - Porgador, A.
AU - Bannerji, R.
AU - Watanabe, Y.
AU - Feldman, M.
AU - Gilboa, Eli
AU - Eisenbach, L.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - IFN-γ genes were introduced through retroviral vectors into the high metastatic, low H-2Kb class I expressor, and poorly immunogenic 3LL-D122 clone. Two types of IFN-γ infectants were isolated: IFN-γ high secretors (128 to 256 IU/ml) and IFN-γ non- or very low secretors (<2 IU/ml). Both manifested high expression of MHC class I Ag. IFN-γ secretors showed significant decrease in tumorigenicity and metastatic growth, whereas IFN-γ nonsecretors retain tumorigenicity and were more metastatic than parental D122 cells. However, both groups, when inoculated in an irradiated form, induced similar high levels of CTL and protected mice to the same degree against a subsequent graft of parental cells. This indicates that enhanced expression of MHC class I and related genes caused by IFN-γ is the major participant in CTL induction. Immunization of mice carrying an established tumor of parental D122 cells with IFN-γ infectants is capable of almost completely preventing lung metastasis. Immunotherapy of tumor-bearing hosts is more effective when IFN-γ secreting cells are used as immunogens, indicating that mechanisms, in addition to CTL, are stimulated by secreted IFN-γ. Moreover, immunization with IFN-γ high secretors of postoperative mice, carrying established micrometastases, almost completely cured these mice. Support for the participation of non-T cell effectors in the response to IFN-γ secretors derives from the reduced tumorigenicity of these cells in CD1 nude mice. These data provide a rationale for the use of IFN-γ gene- transferred tumor cells as a modality for cancer therapy.
AB - IFN-γ genes were introduced through retroviral vectors into the high metastatic, low H-2Kb class I expressor, and poorly immunogenic 3LL-D122 clone. Two types of IFN-γ infectants were isolated: IFN-γ high secretors (128 to 256 IU/ml) and IFN-γ non- or very low secretors (<2 IU/ml). Both manifested high expression of MHC class I Ag. IFN-γ secretors showed significant decrease in tumorigenicity and metastatic growth, whereas IFN-γ nonsecretors retain tumorigenicity and were more metastatic than parental D122 cells. However, both groups, when inoculated in an irradiated form, induced similar high levels of CTL and protected mice to the same degree against a subsequent graft of parental cells. This indicates that enhanced expression of MHC class I and related genes caused by IFN-γ is the major participant in CTL induction. Immunization of mice carrying an established tumor of parental D122 cells with IFN-γ infectants is capable of almost completely preventing lung metastasis. Immunotherapy of tumor-bearing hosts is more effective when IFN-γ secreting cells are used as immunogens, indicating that mechanisms, in addition to CTL, are stimulated by secreted IFN-γ. Moreover, immunization with IFN-γ high secretors of postoperative mice, carrying established micrometastases, almost completely cured these mice. Support for the participation of non-T cell effectors in the response to IFN-γ secretors derives from the reduced tumorigenicity of these cells in CD1 nude mice. These data provide a rationale for the use of IFN-γ gene- transferred tumor cells as a modality for cancer therapy.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027298471&partnerID=8YFLogxK
M3 - Article
C2 - 8432988
AN - SCOPUS:0027298471
VL - 150
SP - 1458
EP - 1470
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -