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Potent Graft Antitumor Effect in Natural Killer-resistant Disseminated Tumors by Transplantation of Interleukin 2-activated Syngeneic Bone Marrow in Mice¹

Kenneth Norris Jr. Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles, California 90033

The current study is a continuation of our previous work showing that bone marrow activated in interleukin 2 has antitumor and antiviral activity in vitro. The antitumor efficacy of IL-2-activated bone marrow cells in vivo was assessed here. Our results indicated that bone marrow cells activated in IL-2 for 3 days (ABM) have antitumor activity in vivo and cause significant tumor regression in mice being treated with ABM and concurrent i.p. administration of IL-2. In mice also bearing larger tumor burdens, those receiving ABM and i.p. IL-2 showed the most significant tumor regression. The ABM seem to be more potent than conventional IL-2-activated spleen lymphokine-activated killer cells. In studies done using lower dosages of IL-2 or log lower number of cells, the ABM caused more significant tumor regression than lymphokine-activated killer cells. We also assessed the antitumor efficacy of short term (1 day) IL-2-activated bone marrow, the short term-activated bone marrow being preferred in bone marrow transplantation because of the minimum amount of cells lost due to its shorter incubation period. We also showed that short term-activated bone marrow caused tumor regression similar to ABM and could reconstitute lethally irradiated mice similar to fresh bone marrow. Therefore, the biomodulation of bone marrow cells could be used as an active therapeutic tool in autologous bone marrow transplantation, producing graft versus tumor effects without any graft versus host effect.

¹ This work is supported by USPHS Grants CA 42962 and CA 01222.

² To whom requests for reprints should be addressed, at Kenneth Norris Jr. Comprehensive Cancer Center, Room 624, 1441 Eastlake Ave., Los Angeles, CA 90033.

Received 2/21/89. Revised 4/28/89. Revised 6/29/89. Accepted 7/13/89.

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