Serum half-life and tumor localization of a chimeric antibody deleted of the C sub H 2 domain and directed against the disialoganglioside GD2

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.15.5702· OSTI ID:6151248

Mueller, B M; Reisfeld, R A ^[1]; Gillies, S D ^[2]

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1. Research Institute of Scripps Clinic, La Jolla, CA (USA)
2. Abbott Biotech, Inc., Needham Heights, MA (USA)

Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. The authors engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors. To this end, the constant region of the human {gamma}1 chain was mutated by deleting the second domain (C{sub H}2). Here the authors show that the C{sub H}2-deleted antibody (ch14.18-{Delta}CH2) was cleared from the blood of athymic (nu/nu) mice bearing human melanoma tumors with the same kinetics as human IgG F(ab{prime}){sub 2}. At a {beta} t{sub 1/2} of 12 hr, 0.9% of the injected dose of {sup 125}I-labeled ch14.18-{Delta}CH2 was found per milliliter of blood 24 hr after i.v. injection. In biodistribution experiments, {sup 125}I-labeled ch14.18-{Delta}CH2 targeted specifically to melanoma xenografts, achieving optimal tumor-to-tissue ratios 12-16 hr after i.v. injection. ch14.18-{Delta}CH2 was localized to the melanoma tumors more rapidly and with better localization ratios than the intact chimeric antibody ch14.18. Sixteen hours after i.v. injection, the tumor-to-blood and tumor-to-liver ratios of ch14.18-{Delta}CH2 were 5 and 12, respectively, while optimal localization ratios obtained for ch14.18 were 1 and 5, respectively, but 96 hr after injection. A reagent such as ch14.18-{Delta}CH2 should be useful for radioimmunodetection of human tumors because of reduced immunogenicity, increased targeting specificity, and rapid clearance from circulation.

• OSTI ID: 6151248
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:15; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIBODIES
TISSUE DISTRIBUTION
NEOPLASMS
RADIOASSAY
BLOOD-PLASMA CLEARANCE
CHIMERAS
DIAGNOSIS
GANGLIOSIDES
GENE RECOMBINATION
IMMUNOLOGY
IODINE 125
MAN
MELANOMAS
MICE
ANIMALS
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CLEARANCE
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GLYCOLIPIDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LIPIDS
MAMMALS
MOSAICISM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PRIMATES
RADIOISOTOPES
RODENTS
SACCHARIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques