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BS Charak, R Agah and A Mazumder
Bone Marrow Transplantation Program, Georgetown University, Washington, DC.
Interleukin-2 (IL-2) therapy generates killer cells with major
histocompatibility complex (MHC)-unrestricted cytotoxicity against most
tumors but not normal tissues. Cyclosporine A (CsA) has been reported to
break tolerance to self and to induce killer cells with specificity against
class II MHC (Ia) antigens both on the host and the tumor cells, resulting
in a mild graft-versus-host disease (GVHD) in an autologous bone marrow
transplantation (BMT) setting in the rat. We used these two agents in a
syngeneic BMT model in a strain of mice that does not develop GVHD with
CsA. Therapy with either agent alone was ineffective, whereas a combination
of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect
against a melanoma and an acute myeloid leukemia. The antitumor effect
could be adoptively transferred by infusing spleen cells harvested from
mice treated with CsA plus IL-2 into secondary recipients that received
chemoradiotherapy. The cytotoxicity of these cells was not influenced by
treatment of tumor cells with gamma-interferon or Ia antibody. The
cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was
no GVHD either in the primary recipients of CsA and IL-2 or in those
receiving the adoptively transferred spleen cells. Our findings show that
combination therapy with CsA and IL-2 after syngeneic BMT induces a potent
GVT effect in a non-MHC-restricted manner, and point to the existence of
differences between the mechanisms of GVT and GVHD.
This article has been cited by other articles:
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| Copyright © 1992 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
