Monoclonal antibody-based therapy of a human tumor xenograft with a 177lutetium-labeled immunoconjugate

Journal Article · Sat Jun 01 04:00:00 EDT 1991 · Cancer Research; (United States)

OSTI ID:5554594

Schlom, J; Siler, K; Milenic, D E; Eggensperger, D; Colcher, D; Miller, L S; Houchens, D; Cheng, R; Kaplan, D; Goeckeler, W ^[1]

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1. National Institutes of Health, Bethesda, MD (USA)

{sup 177}Lutetium ({sup 177}Lu) is a member of the family of elements known as lanthanides or rare earths. Monoclonal antibody (MAb) CC49, a murine IgG1, which is reactive with the tumor-associated antigen, TAG-72, has been shown previously to react with a wide range of human carcinomas; CC49 reacts to a different epitope on the TAG-72 molecule than MAb B72.3 and has a higher binding affinity. We report here the first use of a {sup 177}Lu-labeled immunoconjugate, {sup 177}Lu-CC49, in an experimental therapy model for human carcinoma. {sup 177}Lu-CC49 was shown to delay the growth of established LS-174T human colon carcinomas in athymic mice at a single dose of 50 microCi. Overt toxicity was observed with the administration of approximately 500 microCi of {sup 177}Lu-CC49 in which 5 of 9 mice died of apparent marrow toxicity. A single administration of 200 or 350 microCi of {sup 177}Lu-CC49, however, was shown to eliminate established tumors through the 77-day observation period after MAb administration. Dose fractionation experiments revealed that at least 750 microCi of {sup 177}Lu-CC49 (250 microCi/week for 3 consecutive weeks) was well tolerated in that 9 of 10 mice survived. Moreover, this dose schedule was able to eliminate the growth of relatively large (300 mm3) human colon tumor xenografts in 90% of the animals treated. Single-dose and dose fractionation studies were also carried out with an isotype-matched control MAb, {sup 177}Lu-MOPC-21. In all dose schedules, a large differential was seen between the therapeutic effects of the {sup 177}Lu-CC49 versus that of the {sup 177}Lu-control MAb. The merits and limitations of the use of {sup 177}Lu-labeled immunoconjugates (in particular, {sup 177}Lu-CC49) are discussed in terms of potential novel therapeutics for human carcinoma.

• OSTI ID: 5554594
• Journal Information: Cancer Research; (United States), Journal Name: Cancer Research; (United States) Vol. 51:11; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ACUTE EXPOSURE
ACUTE IRRADIATION
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARCINOMAS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
EXPERIMENTAL NEOPLASMS
FRACTIONATED IRRADIATION
GASTROINTESTINAL TRACT
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
INTESTINES
IRRADIATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LARGE INTESTINE
LUTETIUM 177
LUTETIUM ISOTOPES
MAMMALS
MEDICINE
MICE
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RARE EARTH ISOTOPES
RARE EARTH NUCLEI
RODENTS
SURVIVAL CURVES
THERAPEUTIC USES
THERAPY
TISSUE DISTRIBUTION
USES
VERTEBRATES