Antitumor effects of recombinant interleukin-6 expressed in eukaryotic cells.
In the present study we evaluate the antitumor efficacy of a glycosylated molecule of interleukin-6 (IL-6), which was cloned and expressed in Chinese hamster ovary cells. When tested with two syngeneic murine tumors, the MC38 adenocarcinoma and the MCA106 fibrosarcoma, recombinant IL-6 (rIL-6) significantly reduced the number of day-3 established MC38 lung metastases, but had no effect on MCA106 lung metastases. A similar effect of rIL-6 was seen on day-3 MC38 liver metastases. The antitumor activity mediated by rIL-6 was achieved at doses of the cytokine ranging from 6 micrograms to 150 micrograms/day. There was no correlation between the responsiveness to rIL-6 of these two tumors and their susceptibility, in vitro, to a direct cytostatic effect of the cytokine or the increase in the expression of major histocompatibility complex (MHC) antigens after exposure to rIL-6. However, a correlation was seen between the antitumor response to rIL-6 and the initial number of tumor cells expressing MHC antigens. The possible role of MHC antigens expressed on tumor cells, the generation of MHC-restricted cytotoxic cells and the responsiveness to IL-6 are discussed.
Eisenthal
A
A
Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel.
Kashtan
H
H
Rabau
M
M
Ramakrishna
V
V
Chaitchik
S
S
Skornick
Y
Y
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D006649:Histocompatibility Antigens / Q000032:analysis; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006649:Histocompatibility Antigens; D015850:Interleukin-6; D011994:Recombinant Proteins