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 Kawase, I. Articles by Kishimoto, S. Search for Related Content PubMed PubMed Citation Articles by Kawase, I. Articles by Kishimoto, S.

Combined Therapy of Mice Bearing a Lymphokine-activated Killer-resistant Tumor with Recombinant Interleukin 2 and an Antitumor Monoclonal Antibody Capable of Inducing Antibody-dependent Cellular Cytotoxicity¹

The Third Department of Internal Medicine, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, Osaka-553, Japan

The ability of lymphokine-activated killer (LAK) cells to mediate antibody-dependent cellular cytotoxicity and its efficacy against a LAK-resistant tumor were investigated. Cells of the MH134 murine hepatoma line are scarcely lysed by LAK cells generated in vitro by incubation of C3H/HeN mouse spleen cells with human recombinant interleukin 2 (rIL 2). However, the splenic LAK cells potently lysed the LAK-resistant tumor cells in the presence of 11G2, a monoclonal antibody (MAb) of the IgG1 isotype reactive with a part of MM antigen. Peritoneal cells induced by daily i.p. injections of rIL 2 not only exhibited LAK activity but also mediated antibody-dependent cellular cytotoxicity against MH134 tumor cells in the presence of 11G2. The peritoneal cells exhibiting these cytotoxic activities were found to be nonadherent and nonphagocytic mononuclear cells possessing a similar cell surface phenotype as that of splenic LAK cells, that is Thy-1.2^+-, Lyt-1.1^-, Lyt-2.1^-, and asialo GM₁⁺. Treatment of spleen cells with antibodies and complement before culture with rIL 2 revealed that the phenotype of splenic LAK precursors is Thy-1.2^- and asialo GM₁⁺. The in vivo induction of peritoneal LAK cells in response to i.p. injections of rIL 2 was markedly depressed in C57BL/6 beige mice but was normally accomplished in BALB/c nude mice. Combined therapy of C3H/HeN mice bearing MH134 ascitic tumor with i.p. injection of rIL 2 and 11G2 brought about potent suppression of the tumor growth, resulting in the significant increase in the number of tumor-free mice, whereas neither rIL 2 nor the MAb could exhibit such a potent antitumor effect when used alone. Injection (i.v.) of anti-asialo GM₁ antibody not only blocked the induction of peritoneal LAK cells by rIL 2 but also abrogated the development of the antitumor effect of the combined therapy. These results strongly suggest that combination of antitumor MAbs capable of inducing antibody-dependent cellular cytotoxicity with rIL 2 therapy could result in the generation of potent antitumor effects against LAK-resistant tumors and that asialo GM₁-positive non-T-cell populations including cells of the natural killer cell lineage are essential, at least in part, for development of the antitumor effects of the combined therapy with rIL 2 and MAbs.

¹ Supported by a Grant-in-aid for Cancer Research from the Ministry of Education, Science, and Welfare.

² To whom requests for reprints should be addressed.

Received 9/10/87. Revised 11/25/87. Accepted 12/ 4/87.

This article has been cited by other articles:

				J. G. Berdeja, A. Hess, D. M. Lucas, P. O'Donnell, R. F. Ambinder, L. F. Diehl, D. Carter-Brookins, S. Newton, and I. W. Flinn Systemic Interleukin-2 and Adoptive Transfer of Lymphokine-Activated Killer Cells Improves Antibody-Dependent Cellular Cytotoxicity in Patients with Relapsed B-Cell Lymphoma Treated with Rituximab Clin. Cancer Res., April 15, 2007; 13(8): 2392 - 2399. [Abstract] [Full Text] [PDF]

				H Takahashi, T Nakada, and I Puisieux Inhibition of human colon cancer growth by antibody-directed human LAK cells in SCID mice Science, March 5, 1993; 259(5100): 1460 - 1463. [Abstract] [PDF]