Regional and systemic distribution of anti-tumor x anti-CD3 heteroaggregate antibodies and cultured human peripheral blood lymphocytes in a human colon cancer xenograft

Journal Article · Wed Nov 14 23:00:00 EST 1990 · Journal of Immunology; (USA)

OSTI ID:6168952

Nelson, H; Ramsey, P S; Kerr, L A; McKean, D J; Donohue, J H ^[1]

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1. Mayo Clinic, Rochester, MN (USA)

Anti-tumor antibody (317G5) covalently coupled to an anti-CD3 antibody (OKT3) produces a heteroaggregate (HA) antibody that can target PBL to lyse tumor cells expressing the appropriate tumor Ag. The i.v. and i.p. distribution of radiolabeled HA antibody 317G5 x OKT3 and of radiolabeled cultured human PBL were studied in athymic nude mice bearing solid intraperitoneal tumor established from the human colon tumor line, LS174T. Mice were injected with 125I-labeled HA antibody, 125I-labeled anti-tumor mAb, or 111In-labeled PBL, and at designated timepoints tissues were harvested and measured for radioactivity. 125I-317G5 x OKT3 localized specifically to tumor sites. Tumor radioactivity levels (percent injected dose/gram) were lower with 125I-317G5 x OKT3 HA antibody than with 125I-317G5 anti-tumor mAb, but were similar to levels reported for other anti-tumor mAb. The major difference in radioactivity levels observed between i.v. and i.p. administration of 125I-317G5 x OKT3 was an increase in hepatic radioactivity after i.v. HA antibody administration. HA antibodies produced from F(ab')2 fragments, which exhibit decreased m. w. and decreased Fc receptor-mediated binding, demonstrated improved tumor:tissue ratios as compared to intact antibody HA. 125I-317G5 F(ab')2 x OKT3 F(ab')2 antibody levels were equivalent to intact HA antibody levels in tumor, but were lower than intact HA antibody levels in the blood, bowel, and liver. Tumor:bowel ratios (20:1 at 48 h) were highest when 317G5 F(ab')2 x OKT3 F(ab')2 was injected i.p. Autoradiography confirmed that anti-tumor x anti-CD3 HA antibodies localized specifically to intraperitoneal tumor; that i.p. administered HA antibodies penetrated tumor directly; and that i.v. administered HA antibodies distributed along tumor vasculature.

• OSTI ID: 6168952
• Journal Information: Journal of Immunology; (USA), Journal Name: Journal of Immunology; (USA) Vol. 145:10; ISSN JOIMA; ISSN 0022-1767
• Country of Publication: United States
• Language: English

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
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EXPERIMENTAL NEOPLASMS
GASTROINTESTINAL TRACT
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IMMUNOTHERAPY
INDIUM 111
INDIUM ISOTOPES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
INTESTINES
INTRAPERITONEAL INJECTION
INTRAVENOUS INJECTION
IODINE 125
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LARGE INTESTINE
LYSIS
MAMMALS
MEDICINE
MICE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RODENTS
SPECIFICITY
THERAPY
TUMOR CELLS
VERTEBRATES