Radioimmunotherapy of the GW-39 human colonic tumor xenograft with 131I-labeled murine monoclonal antibody to carcinoembryonic antigen.
We have investigated the therapeutic efficacy of a single injection of 131I-labeled murine mouse monoclonal antibody (NP-4) against carcinoembryonic antigen using the human colonic tumor xenograft, GW-39, grown in the cheek pouches of adult hamsters. Therapeutic efficacy was dependent on the dose of radioactivity, the specificity of the antibody for the tumor, and the size of the tumor when the radioantibody was administered. A dose of 1 mCi of 131I-labeled NP-4 given 1 day after tumor transplantation completely inhibited the growth of 6 of 11 tumors over a 12-week period, and histological evidence indicated that viable tumor was absent in the tissue remaining at the injection site. Lower doses (0.5 mCi) of 131I-labeled NP-4 inhibited tumor growth over 90% in comparison to untreated animals, but the tumors eventually resumed growth. Delaying the administration of radioantibody for 4 or 7 days after tumor transplantation significantly reduced the therapeutic efficacy. Although the same dose of 131I-labeled irrelevant immunoglobulin G also inhibited tumor growth, 131I-labeled NP-4 was generally 2-3 times more effective in reducing tumor growth than was the control IgG. There was a 13% loss in body weight within 7 days after treatment with 1 mCi, but all the animals regained their weight by day 14, indicating that the level of radioactivity was tolerated well. Dosimetric calculations predicted that over 14 days a dose of nearly 2400 rads was delivered to the tumors with 131I-labeled NP-4. These results confirm our previous studies that 131I-labeled antibody can effectively inhibit tumor growth, but suggest that radioantibody therapy is most effectively administered when there is a low tumor burden.
Sharkey
R M
RM
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Pykett
M J
MJ
Siegel
J A
JA
Alger
E A
EA
Primus
F J
FJ
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D005260:Female; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D011879:Radiotherapy Dosage; D014183:Transplantation, Heterologous; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes