INTERLEUKIN 2 (IL-2) IS A RELATIVELY WELL-STUDIED LYMPHOKINE THAT PROMOTES PROLIFERATION AND DIFFERENTIATION OF T LYMPHOCYTES AND NATURAL KILLER CELLS.

INTERLEUKIN 2 (IL-2) IS A RELATIVELY WELL-STUDIED LYMPHOKINE THAT PROMOTES PROLIFERATION AND DIFFERENTIATION OF T LYMPHOCYTES AND NATURAL KILLER CELLS. IL-2 HAS POTENT ANTITUMOR EFFECTS WHEN ADMINISTERED TO EXPERIMENTAL MICE WITH METASTATIC DISEASE. UNFORTUNATELY, INITIAL EFFORTS TO TREAT HUMANS WITH DOSES OF IL-2 COMPARABLE TO THOSE USED IN THE MOUSE LED TO UNACCEPTABLE TOXICITY OF TYPES NOT PREDICTABLE FROM THE KNOWN ACTIONS OF THE LYMPHOKINE. WE PROPOSE TO PRODUCE MOUSE ANTIBODIES THAT BIND TO IL-2 RECEPTORS ON LYMPHOCYTES AND MIMIC IL-2 IN THEIR FUNCTIONAL EFFECTS. SUCH ANTIBODIES SHOULD HAVE A MUCH LONGER HALF-LIFE IN VIVO THAN IL-2 AND SHOULD NOT NECESSARILY PRODUCE THE UNDESIRABLE TOXICITY ASSOCIATED WITH HIGH DOSES OF IL-2. SPECIFICALLY, WE WILL PRODUCE NEUTRALIZING ANTI-IL-2 ANTIBODIES AND THEN GENERATE ANTI-IDIOTYPE ANTIBODIES AGAINST THE NEUTRALIZING IMMUNOGLOBULIN. IL-2 MIMETIC ANTIBODIES WILL BE IDENTIFIED ON THE BASIS OF THEIR ABILITY TO SUPPORT THE GROWTH OF IL-2-DEPENDENT LYMPHOCYTES. UNDER DIFFERENT AEGIS WE HAVE DEVELOPED A SYSTEM FOR RAPID TRANSFER OF VARIABLE REGION IMMUNOGLOBULIN CODING SEGMENTS FROM MURINE TO HUMAN GENES. THEREFORE, IL-2 MIMETIC ANTIBODIES PRODUCED IN MICE COULD BE READILY ADAPTED FOR POTENTIAL USE IN HUMAN THERAPY. SUCH ANTIBODIES COULD BE USED IN VIVO NOT ONLY TO AUGMENT ANTI-TUMOR IMMUNITY BUT ALSO TO AUGMENT IMMUNITY IN PATIENTS WITH IMMUNE DEFICIENCY STATES.