T-cell receptors for cytokines: Targets for immunotherapy of leukemia/lymphoma

1569-8041

adult T-cell leukemia ; anti-Tac mAb ; cytokine ; HTLV-I ; interleukin-2 ; interleukin-15

Springer Online Journal Archives 1860-2000

Medicine

Abstract Background:Cytokine receptors are exceptionally valuable targetsfor immunotherapy. For example, the high affinity IL-2 receptor is expressedby abnormal T cells in patients with certain lymphoid malignancies orautoimmune disorders and in individuals rejecting allografts whereas it is notexpressed by normal resting cells. Design:To exploit this difference in receptor expression innormal resting cells and leukemic cells we have introduced different forms ofIL-2 receptor directed therapy including an unmodified murine antibody to theα subunit of the IL-2 receptor (anti-Tac), humanized anti-Tac as well asthis antibody armed with truncated Pseudomonasexotoxin or α- andβ-emitting radionuclides (e.g., 211At and 90Y). Inparticular, unmodified murine anti-Tac was used in the therapy ofHTLV-I-associated adult T-cell leukemia (ATL). Results:Six of nineteen patients treated with this antibodyunderwent a partial (four) or complete (two) remission. In a subsequentclinical trial involving anti-Tac armed with 90Y over 50%of the patients with ATL treated underwent a partial or complete remission. Conclusions:New agents under development include humanizedantibodies directed toward shared cytokine receptors such as IL-2/15Rβused by both IL-2 and IL-15 as well as to a shared signal transduction elementJak3 utilized by the T-cell stimulatory cytokines IL-2, IL-4, IL-7, IL-9 andIL-15. Thus our emerging understanding of cytokine receptors and theirsignaling pathways taken in conjunction with the ability to produce humanizedantibodies armed with radionuclides or toxins are providing novel perspectivesfor the treatment of leukemia and lymphoma.

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