Phase Ia trial of murine immunoglobulin A antitransferrin receptor antibody 42/6

In preclinical in vitro and in vivo systems, mAbs to human transferrin (Tf) receptors blocked iron uptake from Tf and showed antitumor activity. However, Tf receptors are also displayed by normal tissues, and a large, soluble pool of circulating serum Tf receptors has been detected. We report result...

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Bibliographic Details
Published in:Clinical cancer research 1995-11, Vol.1 (11), p.1259-1265
Main Authors: BROOKS, D, TAYLOR, C, DOS SANTOS, B, LINDEN, H, HOUGHTON, A, HECHT, T. T, KORNDELD, S, TAETLE, R
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal - therapeutic use
Antineoplastic agents
Biological and medical sciences
Bone Marrow - drug effects
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
Female
Humans
Immunoglobulin A - adverse effects
Immunoglobulin A - blood
Immunoglobulin A - therapeutic use
Leukocytes, Mononuclear - metabolism
Male
Medical sciences
Mice
Middle Aged
Neoplasms - blood
Neoplasms - immunology
Neoplasms - therapy
Pharmacology. Drug treatments
Receptors, Transferrin - immunology
Receptors, Transferrin - metabolism
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Summary:In preclinical in vitro and in vivo systems, mAbs to human transferrin (Tf) receptors blocked iron uptake from Tf and showed antitumor activity. However, Tf receptors are also displayed by normal tissues, and a large, soluble pool of circulating serum Tf receptors has been detected. We report results of a Phase Ia trial of IgA monoclonal anti-Tf receptor antibody 42/6. Twenty-seven patients with advanced refractory cancer received 33 treatments with 42/6 administered as a 24-h infusion at doses ranging from 2.5 to 300 mg/m2. 42/6 was generally well tolerated, although one patient receiving a second treatment experienced an allergic-type response associated with a human antimouse antibody response. Three patients with hematological cancers showed mixed tumor responses; there were no partial or complete remissions. Peak serum levels of antibody were obtained at the termination of the 24-h infusion. At doses >/=25 mg/m2, there was a linear relationship between the 42/6 dose and average peak serum 42/6 levels ranging from
ISSN:1078-0432
1557-3265