We infused the murine monoclonal antibody T101 into two patients with advanced refractory chronic lymphocytic leukemia (CLL) after confirming its reactivity with their CLL cells. One patient received doses of 1, 3, and 12 mg; the second patient received 10 mg. Antibody was delivered over 10--15 min. The major observations were: (1) T101 murine monoclonal antibody did bind to cells with T65 surface antigen and saturated these cells in vivo; (2) cells that bound T101 disappeared from the circulation by 2 hr after treatment, as evidenced by a marked drop in lymphocyte counts; (3) T101 serotherapy resulted in some intravascular cell injury associated with sequestration and probably destruction in the liver and lung; (4) free serum T101 was demonstrable, but disappeared by 2--4 hr after infusion; (5) rapid infusion of T101 did not induce significant modulation of T65; (6) rapid infusion of greater than 10 mg of T101 was associated with significant systemic reactions. Monoclonal antibodies may someday have an application in leukemia therapy, but additional experimental trials are clearly indicated.
The expression of shared idiotypes (Slds) has been studied on malignant CD5+B cells from patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) using a panel of 37 murine monoclonal antibodies previously demonstrated to be reactive with Slds derived from follicular B-cell lymphomas. Thirteen anti-Slds identified tumor cells from 31 of 105 (30%) CLL patients and 4 of 6 SLL patients. In comparison, the same panel of anti-Slds is reactive with 33% of follicular and diffuse B-cell lymphomas. Ten of these anti-Slds reacted with CLL cases at similar frequencies to that of the B-cell lymphomas. Two anti-Slds, which are known to react with autoantibodies, were significantly more prevalent in CLL than in B-cell lymphomas. These data confirm the presence of Slds in CLL and provide further evidence of an association between CLL and autoimmunity. The identification of a panel of antibodies reactive with a significant number of CLL and SLL patients will facilitate the application of anti-idiotype antibody therapy in these diseases.
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