The effect of radiosensitizers on radio-immunotherapy, using 131I-labelled anti-CEA antibodies in a human colonic xenograft model.
Anti-CEA antibodies were used for radio-immunotherapy in an established LS174T colonic xenograft in nude mice. A single IV dose of either 131I-PK4S (polyclonal) or -A5B7 (monoclonal) antibody produced tumour regression, and significantly delayed subsequent tumour growth. Administration of a clearing second antibody, 24 hr post 131I-PK4S and at 5 times the dose, significantly reduced the therapeutic effect of radio-antibody alone. Tumours of mice given non-specific antibody or unlabelled anti-CEA antibody grew like those of untreated controls. In an attempt to enhance therapy without increasing dose, radiosensitizers normally employed with external beam radiation were used in combination therapy. When the hypoxic cell radiosensitizer misonidazole was combined with 131I-A5B7, it significantly prolonged tumour-growth inhibition over radio-antibody alone. Conversely, the therapeutic effect of either radio-antibody was significantly reduced when used in combination with the halogenated pyrimidine radiosensitizer 5-iododeoxyuridine. Neither sensitizer alone affected tumour growth.
Pedley
R B
RB
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Begent
R H
RH
Boden
J A
JA
Boden
R
R
Adam
T
T
Bagshawe
K D
KD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000628:therapy*; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008657:Metabolic Clearance Rate; D051379:Mice; D008920:Misonidazole / Q000008:administration & dosage / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
C518613:A5B7 monoclonal antibody; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D008920:Misonidazole; D007065:Idoxuridine