TY - JOUR
T1 - DAB389IL2 (ONTAK®) fusion protein therapy of chronic lymphocytic leukaemia
AU - Frankel, Arthur E.
AU - Fleming, Donald R.
AU - Powell, Bayard L.
AU - Gartenhaus, Ronald
PY - 2003/2
Y1 - 2003/2
N2 - Despite multiple new therapeutic options for patients with chronic lymphocytic leukaemia (CLL), the prognosis of patients with relapsed disease is poor. After first-line therapy with fludarabine, alkylating agents, rituximab or combinations of these agents, most patients relapse within a few years. While second-line therapy with alemtuzumab, or other combinations of the above agents, have produced remissions, most of these are partial responses lasting months rather than years. Patients commonly die from progressive disease or infections related to the underlying disease or treatment. The authors sought to develop a novel therapeutic with the capacity to kill chemotherapy-resistant CLL cells and with reduced toxicities to normal tissues. Based on the presence of high affinity interleukin-2 receptor (IL-2R) on CLL cells, therapy of relapsed CLL patients with a diphtheria fusion protein targeting IL-2R - DAB389IL2 (ONTAK®, Seragen, Inc., Hopkinton, MA, USA) - was tested in a pilot Phase II study. Biological activity and a partial remission were observed with modest drug-related side effects. Based on these encouraging findings, alternative schedules and combinations with agents that may enhance CLL cell expression of IL-2R are being tested. Hopefully, the use of these targeted therapeutic approaches will provide additional therapeutic options with fewer side effects for this common and incurable condition.
AB - Despite multiple new therapeutic options for patients with chronic lymphocytic leukaemia (CLL), the prognosis of patients with relapsed disease is poor. After first-line therapy with fludarabine, alkylating agents, rituximab or combinations of these agents, most patients relapse within a few years. While second-line therapy with alemtuzumab, or other combinations of the above agents, have produced remissions, most of these are partial responses lasting months rather than years. Patients commonly die from progressive disease or infections related to the underlying disease or treatment. The authors sought to develop a novel therapeutic with the capacity to kill chemotherapy-resistant CLL cells and with reduced toxicities to normal tissues. Based on the presence of high affinity interleukin-2 receptor (IL-2R) on CLL cells, therapy of relapsed CLL patients with a diphtheria fusion protein targeting IL-2R - DAB389IL2 (ONTAK®, Seragen, Inc., Hopkinton, MA, USA) - was tested in a pilot Phase II study. Biological activity and a partial remission were observed with modest drug-related side effects. Based on these encouraging findings, alternative schedules and combinations with agents that may enhance CLL cell expression of IL-2R are being tested. Hopefully, the use of these targeted therapeutic approaches will provide additional therapeutic options with fewer side effects for this common and incurable condition.
KW - Chronic lymphocytic leukemia
KW - Diphtheria fusion protein
KW - Interleukin-2 receptor
UR - http://www.scopus.com/inward/record.url?scp=0037322572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037322572&partnerID=8YFLogxK
U2 - 10.1517/eobt.3.1.179.20959
DO - 10.1517/eobt.3.1.179.20959
M3 - Review article
C2 - 12718740
AN - SCOPUS:0037322572
SN - 1471-2598
VL - 3
SP - 179
EP - 186
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 1
ER -