A PILOT CLINICAL-TRIAL OF 2 MURINE MONOCLONAL-ANTIBODIES FIXING HUMAN-COMPLEMENT IN PATIENTS WITH CHRONIC LYMPHATIC-LEUKEMIA

Citation
S. Greenaway et al., A PILOT CLINICAL-TRIAL OF 2 MURINE MONOCLONAL-ANTIBODIES FIXING HUMAN-COMPLEMENT IN PATIENTS WITH CHRONIC LYMPHATIC-LEUKEMIA, Leukemia & lymphoma, 13(3-4), 1994, pp. 323-331
Citations number
NO
Categorie Soggetti
Hematology
Journal title
ISSN journal
10428194
Volume
13
Issue
3-4
Year of publication
1994
Pages
323 - 331
Database
ISI
SICI code
1042-8194(1994)13:3-4<323:APCO2M>2.0.ZU;2-N
Abstract
The use of monoclonal antibodies (MABs) for the therapy of malignant d iseases offers the potential advantage of greater target cell specific ity, and therefore less toxicity. A major limitation of this therapeut ic approach has been the inability of most MABs to kill the cell once bound to the target antigen. We have previously reported the developme nt of two murine IgM MABs, WM63 (CD48) and WM66 (unclustered), that re act with panleucocyte antigens widely expressed on cells from lymphopr oliferative disorders, and are lytic with human complement. These anti bodies have subsequently been administered intravenously to patients w ith chronic lymphocytic leukaemia (CLL) in a Phase One trial. Seven pa tients with progressive CLL received increasing daily doses of WM66 (P atients 1-3) or WM63 (Patients 4-7), with one patient also receiving a continuous infusion of WM63 over 20 hours. All patients demonstrated a significant but transient reduction in the number of circulating leu cocytes, and no overall effect on disease progression was observed. An tibody coating of circulating lymphocytes was seen in patients receivi ng WM-63. Patients receiving large doses of WM63 (cases 5-7) demonstra ted a decline in complement levels during treatment. There were no maj or adverse reactions to WM66, but two patients developed dose limiting side effects to WM63. No human anti-mouse antibody (HAMA) responses w ere documented. These findings indicate that in vitro cytotoxicity med iated by Mabs fixing human complement correlates poorly with clinical responses, and support earlier observations which indicate that cell-m ediated cytotoxicity is necessary for effective antibody therapy.