EXAMINATION OF A ROLE FOR IDIOTYPY IN THE DISEASE REMISSION OF A LONG-TERM SURVIVOR ADULT T-CELL LEUKEMIA TREATED WITH ANTI-TAC ANTIBODY

The alpha chain of the interleukin 2 receptor (IL2R alpha; Tac) was ta rgeted in clinical trials with adult T cell leukemia using murine anti -Tac antibody. Of 19 patients, a single individual achieved a durable complete remission. The mechanism of this action by murine anti-Tac ha s not been defined. We examined the hypothesis that the maintenance of the long-term response after treatment might be related to induction of a network of anti-idiotypic antibodies, as proposed in other tumor settings. In contrast to anti-Tac non-responders, the patient was foun d to have produced a human anti-mouse antibody (HAMA) response, and sp ecifically an anti-idiotypic (Ab2) response, that was readily detectab le by standard assays 4 years after treatment. Using phage display ant ibody libraries, this response was shown to be monoclonal, consisting of a single IgG1,kappa antibody of moderate affinity. No evidence was found for anti-anti-idiotypic (Ab3) antibodies with reactivity for sTa c, which might alternatively have maintained an autogenic human anti-T ac antibody response. An area of limited homology was noted between th e Ab2 antibody and the IL2R in the domain of IL2 binding, but no bindi ng of Ab2 to IL2 could be shown that might have reduced endogenous lig and (IL2) concentrations. Similarly, no anti-anti-idiotypic (T3) T cel l response was detected. Thus, we are unable to confirm features of id iotypy that could suggest a role in maintaining an anti-tumor response by anti-Tac antibody therapy.