Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma

Journal Article · Thu Mar 01 04:00:00 EST 1990 · Journal of Clinical Oncology; (USA)

DOI:https://doi.org/10.3109/07357909009017592· OSTI ID:6969352

Steis, R G; Carrasquillo, J A; McCabe, R; Bookman, M A; Reynolds, J C; Larson, S M; Smith, J.W. 2d.; Clark, J W; Dailey, V; Del Vecchio, S ^[1]

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1. National Cancer Institute-Frederick Cancer Research Facility, MD (USA)

Two human immunoglobulin M (IgM) monoclonal antibodies (MoAbs), 16.88 and 28A32, which react with cytoplasmic (28A32 and 16.88) or cell surface (28A32) determinants on human colon carcinoma cells, were administered intravenously to 26 patients with metastatic colorectal carcinoma to determine if they could localize to sites of metastatic disease, if they had any antitumor or toxic effects, and to determine whether they would elicit an antihuman MoAb response. Serial scans showed tumor uptake of radioisotope in 12 of 16 patients receiving 131I-labeled 28A32 and in nine of 12 patients receiving 131I-labeled 16.88. No antitumor effects were seen with either antibody. No antibody-related toxic effects were observed following administration of 16.88, but two patients developed localized urticarial reactions following injection with antibody 28A32. No patient developed an antibody response to 16.88. Anti-28A32 reactivity was found in five of 12 (42%) normal sera and in seven of 23 (30%) patients before receiving any antibody. Following administration of 28A32, a low titer (1:10 dilution) of anti-28A32 developed in four patients with no preexisting antibody, a decrease in the preexisting titer was seen in three other patients, the titer remained constant in one patient, and no anti-28A32 was ever detected in six patients. In most cases, anti-28A32 activity was lost at dilutions greater than 1:10 and did not appear to affect antibody half-life in the serum or whole body retention of the antibody. We conclude that these human IgM MoAbs are capable of localizing at sites of disease in vivo, are nontoxic, and are poorly immunogenic in humans. Further studies to determine the specificity of targeting and to improve the delivery of antibody to sites of tumor are indicated.

• OSTI ID: 6969352
• Journal Information: Journal of Clinical Oncology; (USA), Journal Name: Journal of Clinical Oncology; (USA) Vol. 8:3; ISSN JCOND; ISSN 0732-183X
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
ANTIGEN-ANTIBODY REACTIONS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOASSAY
BIOLOGICAL LOCALIZATION
BODY
CARCINOMAS
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DISEASES
GASTROINTESTINAL TRACT
IMMUNOASSAY
IMMUNOLOGY
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 131
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LARGE INTESTINE
METASTASES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PATIENTS
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOISOTOPES
RECTUM
TRACER TECHNIQUES