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Monoclonal antibody T101 in T cell malignancies: a clinical,
pharmacokinetic, and immunologic correlation
JH Bertram, PS Gill, AM Levine, D Boquiren, FM Hoffman, P Meyer and MS Mitchell
Eight patients with cutaneous T cell lymphomas (CTCL) and five with various
other T cell malignancies were treated with mouse monoclonal antibody
(MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour
period and resulted in one complete remission (convoluted T cell lymphoma)
and one partial remission (CTCL). Remission duration was 6 weeks and 3
months, respectively. Frequent toxicities were pruritus, hives, flushing,
and shortness of breath. Supraventricular arrhythmias and blood pressure
instability were also observed. Complete targeting of peripheral blood T
cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less
than 10,000/microL), and free, bioavailable antibody was present at the
next (10-mg) dose level. Even higher doses resulted in substantial antibody
excess that persisted for as long as 6 weeks. Serum concentrations of MoAb
decreased with increasing number of peripheral blood T cells, and 25 to 35
mg of T101 were required for induction of antibody excess in leukemic
patients. Excess antibody induced antigenic modulation, which was of
consequence only if MoAb excess persisted to the next treatment. In the
original treatment, the rapidly administered MoAb was able to target and
remove peripheral blood T cells before the development of antigenic
modulation. Antimouse antibodies developed in three patients. Their
presence rendered further therapy ineffective and was associated with an
anaphylactic reaction in one patient. Development of these antibodies could
not be predicted by lymphoproliferative assays. In these assays, however,
the T101 protein strongly stimulated the mononuclear cells of the patient
who reached the only complete remission of this trial. Immunologic
stimulation by the MoAb thus might have played a role in this patient's
antitumor response. In summary, therapy with MoAb T101 was specific but
only modestly efficacious. Rapid infusion of nonmodulating doses of
antibody provided excellent targeting and removal of peripheral blood T
cells and might be a valid approach in future trials with immunoconjugated
T101.
Volume 68,
Issue 3,
pp. 752-761,
09/01/1986
Copyright © 1986 by The American Society of Hematology
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