A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: Effects of tumor burden and antigen expression

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Clinical Oncology; (USA)

OSTI ID:7015005

Scheinberg, D A; Straus, D J; Yeh, S D; Divgi, C; Garin-Chesa, P; Graham, M; Pentlow, K; Coit, D; Oettgen, H F; Old, L J ^[1]

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1. Memorial Sloan-Kettering Cancer Center, New York, NY (USA)

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

• OSTI ID: 7015005
• Journal Information: Journal of Clinical Oncology; (USA), Journal Name: Journal of Clinical Oncology; (USA) Vol. 8:5; ISSN JCOND; ISSN 0732-183X
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOPSY
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
IMMUNE SYSTEM DISEASES
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
IODINE 131
IODINE ISOTOPES
ISOTOPES
LEUKOCYTES
LYMPHOCYTES
LYMPHOMAS
MATERIALS
MEDICINE
METABOLISM
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
PATIENTS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
SOMATIC CELLS
THERAPY
TISSUE DISTRIBUTION
UPTAKE