DAB(389)IL-2 (
denileukin diftitox,
ONTAK) is an
interleukin-2 receptor (IL-2R)-specific
ligand fusion
protein that may potentially be selective for IL-2R-expressing
malignancies. The activity of
DAB(389)IL-2 in the treatment of
cutaneous T-cell lymphoma has established the feasibility of utilizing such a targeted therapeutic in disseminated disease with acceptable toxicity. Data from the phase I trial suggest that the definition of activity in other
cancer types, including other non-Hodgkin's
lymphomas (NHL), is warranted. Three NHL patients in this study responded, two of whom had
follicular lymphomas, with the third having a primary intermediate-grade B-cell NHL that was refractory to
chemotherapy and stem cell transplant. This patient has remained
in complete remission over 3 years
after treatment with
DAB(389)IL-2. Patients treated to date have had IL-2R-positive
tumors, but this remains a very complex clinical issue. The need for a threshold level of receptor expression, the difficulty in obtaining representative tissue, the lack of an assay that accurately reflects high-affinity receptor, and the potential difficulty of observer variability in evaluating the assays should point us toward examining response rates in
cancer patients where IL-2R cannot be detected or is unknown. The potential to target the high-affinity IL-2R supports the development of this agent in
transplantation and in
autoimmune diseases. Targeting IL-2R-expressing lymphocytes may be an effective strategy for the prevention of graft rejection and to treat or prevent
graft-versus-host disease.
DAB(389)IL-2 has been examined in clinical trials of
psoriasis and
rheumatoid arthritis and has shown promising results. The potential utility in other autoimmune disorders is unknown, but diseases such as systemic lupus, scleroderma, and
vasculitis also may be effective candidates for such
ligand fusion
therapy.