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Adoptive Immunotherapy by Pantropic Killer Cells Recovered from OK-432-injected Tumor Sites in Mice¹

Central Research Laboratories, Chugai Pharmaceutical Co., 3-41-8 Takada, Toshima-ku, Tokyo 171 [M. S., M. N., M. K., Y. M., Y. S.]; Tokyo Institute for Immunopharmacology, Takada, Toshimaku, Tokyo 171 [M. S., T. Y.]; and Tohoku University, 2-1 Seiryo-machi, Sendai 980 [N. I.]; Japan

A murine malignant ascites model with BAMC-1 tumors was established previously, which was cured completely by five consecutive i.p. injections of OK-432. We have found that peritoneal mononuclear cells from these animals contained antitumor effector cells which could destroy nonspecifically a variety of tumor cells in vitro. They were tentatively called pantropic killer cells (PKCs). The present study was essentially designed to show the antitumor effectiveness of the PKCs in vivo by the use of an adoptive immunotherapy model. The growth of BAMC-1 tumors transplanted s.c. 5 days earlier was significantly suppressed by passive transfer of 5 x 10⁶ to 2 x 10⁷ PKCs induced by injection of OK-432 into BAMC-1 bearing donor mice, while more than 1 x 10⁸ immune spleen cells from the same donors treated with OK-432 were required to achieve the similar effects. Furthermore, if the tumor-bearing recipients were pretreated with 180 mg/kg of cyclophosphamide 1 h before the adoptive transfer, even 5 x 10⁶ PKCs could induce complete regression of the tumors transplanted 5 days earlier. This protocol made it possible even to achieve the complete regression of larger tumors (9–10 mm in diameter) in recipients transplanted 12 days earlier. The PKCs were, as expected, able to cure not only BAMC-1-bearing animals but also Meth-A-bearing mice. As effector cells for adoptive immunotherapy, therefore, the PKCs induced by OK-432 seem to be as effective as, if not better than, lymphokine-activated killer cells expanded in vitro by culturing tumor infiltrating lymphocytes with interleukin-2. Although the study on surface markers of PKCs did not unequivocally discriminate these from lymphokine-activated killer cells, the present findings are considered significant indicating that a potent biological response modifier such as OK-432 can induce pantropic killer cells which are extremely effective in destroying various tumor cells in vivo. One of the advantages of OK-432 therapy over lymphokine-activated killer cell therapy, therefore, is that the former does not require the tedious and time-consuming in vitro procedures which are essential for the latter.

¹ The data in this article were partly presented at the Satellite Symposium of Japanese Society for Cancer Therapy at Matsue, Japan, October 1986.

² To whom requests for reprints should be addressed.

Received 11/ 9/87. Revised 3/23/88. Accepted 4/29/88.

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