This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reid, T. R. Articles by Basham, T. Y. Search for Related Content PubMed PubMed Citation Articles by Reid, T. R. Articles by Basham, T. Y.

Enhanced in Vivo Therapeutic Response to Interferon in Mice with an in Vitro Interferon-resistant B-Cell Lymphoma¹

Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, California 94305 [T. R. R., E. R. R., B. H. W., T. C. M., T. Y. B.], Department of Pathology, Uniformed Services School of Medicine, Bethesda, Maryland 20014 [R. M. F.]

A stable subline of 38C13 B-cell lymphoma (SIR-1) resistant to the antiproliferative effects of -interferon (IFN) was isolated. In addition to defects in antiproliferative effects of IFN, SIR-1 is defective in IFN-mediated antiviral activity against both encephalomyocarditis virus and vesicularstomatitis virus. It is also defective in the induction of 2'-5'-oligoadenylate synthetase mRNA and enzyme activity, enhancement of H-2 antigen expression, and transient induction and subsequent repression of c-myc by IFN. SIR-1, although completely resistant to IFN in vitro, is more sensitive to IFN than the parental cell line in vivo. IFN treatment at 10⁴ units, three times weekly, resulted in a 28% increase in mean survival time and a 1.4% long term survival rate in the IFN-sensitive 38C13 cell line but resulted in a 275% increase in mean survival rate and a 27% long term survival rate in the interferon-resistant SIR-1 mutant. Statistical analysis of 38C13 and SIR-1 with and without IFN treatment demonstrate that: a) the SIR-1 mutant remains sensitive to the cytotoxic effects of IFN in vivo (P < 0.0001); and b) the mean survival and long term survival of animals with the SIR-1 mutant is significantly greater than for animals with the IFN-sensitive 38C13 cell line (P < 0.0001). Two additional independently isolated IFN-resistant cell lines (SIR-111 and SIR-E102) also demonstrate significantly enhanced in vivo response to IFN compared to the interferon-sensitive parental (38C13) cells. These results indicate that, for this cell line, the antitumor effects of IFN are mediated by activation of host defenses and that resistance to the in vitro cytotoxic effects of IFN results in a tumor phenotype that is more readily recognized by host defenses and eliminated.

¹ This work was supported by the National Foundation for Cancer Research and Grants CA 34233 and ST32-09302 from the National Cancer Institute. A special thanks goes to the N. H. Leong Memorial Scholarship Fund which provided T. R. R. with funds to pursue this work while studying medicine.

² To whom requests for reprints should be addressed, at S-140, Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305.

Received 11/16/88. Revised 3/ 9/89. Accepted 5/ 3/89.

This article has been cited by other articles:

				T.-H. Huang, K. R. Chintalacharuvu, and S. L. Morrison Targeting IFN-{alpha} to B Cell Lymphoma by a Tumor-Specific Antibody Elicits Potent Antitumor Activities J. Immunol., November 15, 2007; 179(10): 6881 - 6888. [Abstract] [Full Text] [PDF]