Preclinical and phase I studies of monoclonal antibodies in melanoma: Application to boron neutron capture therapy of melanoma

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Pigment Cell Research; (USA)

DOI:https://doi.org/10.1111/j.1600-0749.1989.tb00202.x· OSTI ID:5157256

Hersey, P ^[1]

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1. Mater Misericordiae Hospital, Royal Newcastle Hospital (Australia)

Monoclonal antibodies (MAbs) provide an attractive method of selectively localizing sufficient boron atoms around tumour cells to capture neutrons. Assuming that 10(8)-10(10) 10B atoms are needed for one capture event and that 10(3)-10(4) atoms can be coupled to each antibody molecule, then 10(5)-10(6) antibody molecules gathered on an individual cell will destroy that cell. Binding to normal tissues, on the other hand, would need to be at least 20-fold less than that to tumour tissues to avoid toxic effects of neutrons on surrounding tissues. Preclinical studies in animals show that several MAbs may bind to melanoma cells in sufficient quantities in vitro to localize the required amount of boron per cell. Whether this will occur in vivo, however, may depend not only on antigen density but a variety of other properties of the tumour cells and MAbs. These include the Ig class and affinity of the antibody and whether the antibody is internalized into the tumour cell. The ratio of uptake between tumour and normal tissue is governed by such factors as the percentage of tumour cells within a tumour expressing the antigen and whether the MAb react with normal tissues. Use of Fab or F(ab)2 preparations of the MAb may increase the uptake ratio by preventing uptake of MAb by cells with Fc receptors. In contrast to preclinical animal studies, tumour/normal tissue uptake ratios in phase I studies in humans have been disappointingly low.80 references.

• OSTI ID: 5157256
• Journal Information: Pigment Cell Research; (USA), Journal Name: Pigment Cell Research; (USA) Vol. 2:4; ISSN 0893-5785; ISSN PCREE
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTIBODIES
BEAMS
BORON 10
BORON ISOTOPES
CELL KILLING
DISEASES
DOCUMENT TYPES
EXPERIMENTAL NEOPLASMS
IMMUNOLOGY
IMMUNOTHERAPY
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MEDICINE
MELANOMAS
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NEUTRON BEAMS
NEUTRON CAPTURE THERAPY
NEUTRON THERAPY
NUCLEAR MEDICINE
NUCLEI
NUCLEON BEAMS
ODD-ODD NUCLEI
PARTICLE BEAMS
PRIMATES
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOLOGY
RADIOTHERAPY
REVIEWS
RODENTS
SPECIFICITY
STABLE ISOTOPES
THERAPY
TUMOR CELLS
VERTEBRATES