Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice.

Abstract

A murine model for acute myeloid leukemia (mAML) was used to study graft-vs.-leukemia (GVL) effects on residual leukemic cells across both major (MHC) and minor histocompatibility antigens (mHA) barriers. In addition, the therapeutic effect of recombinant human interleukin-2 (rhIL-2)-administered postsyngeneic and allogeneic bone marrow transplantation (BMT) was examined. SJL/J mice inoculated with mAML cells were exposed later to total body irradiation (TBI) and transplanted with bone marrow cells (BMC) mixed with spleen cells derived from normal syngeneic (SJL/J), congenic (B10.S), or allogeneic (C57BL/6) donor mice. One-half of the mice in each group received low dose rhIL-2 for 3 days starting 1 day post-BMT. Spleen cells from treated recipients were transferred to secondary naive SJL/J mice for in vivo detection of residual tumor cells. At a tumor load of 10(5) cells per animal, none of the mice rescued with SJL/J or B10.S cells was cured since 100% of secondary recipients developed leukemia. Concomitant treatment of recipients of B10.S cells with rhIL-2 induced GVL effects since none of the secondary recipients developed leukemia after 2 years. All adoptive recipients of mice rescued with C57BL/6 cells remained free of leukemia after 2 years whether or not rhIL-2 was injected. The potency of the GVL effects observed across mHA and MHC were tumor-cell dose dependent since fewer animals inoculated with 10(6) mAML cells were cured. Only marginal GVL effects were noticed following syngeneic BMT and rhIL-2. Our results sustain the importance of the GVL effects in the treatment of myeloid leukemia and demonstrate that immunotherapy with rhIL-2 following BMT can enhance the therapeutic effect induced by the allograft.

• Authors: U Vourka-Karussis, D Karussis, A Ackerstein, S Slavin
• Journal: Experimental hematology (Exp Hematol) Vol. 23 Issue 3 Pg. 196-201 (Mar 1995) ISSN: 0301-472X [Print] Netherlands
• PMID: 7875238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Interleukin-2
• Receptors, Interleukin-2
• Recombinant Proteins

Topics

• Animals
• Bone Marrow Transplantation
• Cell Division (drug effects)
• Cell Transplantation
• Cells, Cultured
• Disease Models, Animal
• Female
• Graft Survival
• Histocompatibility Testing
• Immunotherapy, Adoptive
• Interleukin-2 (pharmacology)
• Leukemia, Myeloid, Acute (chemically induced, pathology, therapy)
• Mice
• Mice, Inbred C57BL
• Receptors, Interleukin-2 (biosynthesis)
• Recombinant Proteins (pharmacology)
• Spleen (pathology)