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 Papa, M. Z. Articles by Rosenberg, S. A. Search for Related Content PubMed PubMed Citation Articles by Papa, M. Z. Articles by Rosenberg, S. A.

Antitumor Efficacy of Lymphokine-activated Killer Cells and Recombinant Interleukin 2 in Vivo: Successful Immunotherapy of Established Pulmonary Metastases from Weakly Immunogenic and Nonimmunogenic Murine Tumors of Three Distinct Histological Types

Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892

We have recently shown that the systemic administration of lymphokine activated killer cells (LAK cells) plus relatively low doses of recombinant interleukin 2 (RIL-2) or the administration of high doses of RIL-2 alone can reduce the number of established pulmonary metastases from the weakly immunogenic MCA-105 sarcoma in mice. We have now analyzed the therapeutic efficacy of these treatments on both weakly and nonimmunogenic tumors of three distinct histological types in two different mouse strains. In all experiments, LAK cells were administered i.v. on days 3 and 6 and RIL-2 was injected i.p. from days 3 through 8 after tumor induction. The MCA-101 sarcoma was completely nonimmunogenic as defined by its inability to successfully immunize C57BL/6 mice. Nevertheless, administration of LAK cells plus 7,500–10,000 units RIL-2 was highly effective in reducing the number of established 3-day pulmonary metastases from this sarcoma [at 7,500 units RIL-2, mean number of metastases 37 ± 11 (SE); P < 0.05; at 100,000 units, 2 ± 1; P < 0.05] when compared to Hanks' balanced salt solution treated control animals (116 ± 9). Likewise, RIL-2 alone at doses of 20,000 units/injection or greater had significant antimetastatic effects (77 ± 12; P < 0.05). Established 3-day pulmonary metastases from the MCA-38 adenocarcinoma in C57BL/6 mice and the M-3 melanoma in C3H mice were also susceptible to adoptive immunotherapy with LAK cells plus RIL-2 and with high dose RIL-2 alone. Treatment of mice with LAK cells alone or with low doses of RIL-2 alone (20,000 units/injection) had little if any antitumor effects.

LAK cells were tested for cytolytic activity in vitro against tumor target cells of a variety of histological types; there was no discernible relationship between susceptibility to lysis by LAK cells in vitro and therapeutic efficacy in vivo.

These findings have thus demonstrated that the successful immunotherapy of established pulmonary metastases with LAK cells plus RIL-2 or with high dose RIL-2 alone includes: (a) tumors that are immunogenic and nonimmunogenic; (b) tumors of distinct histological types such as sarcoma, adenocarcinoma, and melanoma; and (c) tumors in at least two different mouse strains, C57BL/6 and C3H, and that there is little correlation between the in vitro lysability of tumor cells by LAK effectors and the susceptibility of these same tumors to successful immunotherapy in vivo.

¹ To whom requests for reprints should be addressed, at Surgery Branch, National Cancer Institute, Building 10, Room 2B42, Bethesda, MD 20892.

Received 3/31/86. Revised 6/25/86. Accepted 6/30/86.

This article has been cited by other articles:

				J. Kjaergaard and S. Shu Tumor Infiltration by Adoptively Transferred T Cells Is Independent of Immunologic Specificity but Requires Down-Regulation of L-Selectin Expression J. Immunol., July 15, 1999; 163(2): 751 - 759. [Abstract] [Full Text] [PDF]