Radioimmunotherapy of human colon carcinoma by 131I-labelled monoclonal anti-CEA antibodies in a nude mouse model.
A mixture of 3 MAbs directed against 3 different CEA epitopes was radiolabelled with 131I and used for the treatment of a human colon carcinoma transplanted s.c. into nude mice. Intact MAbs and F(ab')2 fragments were mixed because it had been shown by autoradiography that these 2 antibody forms can penetrate into different areas of the tumor nodule. Ten days after transplantation of colon tumor T380 a single dose of 600 microCi of 131I MAbs was injected i.v. The tumor grafts were well established (as evidenced by exponential growth in untreated mice) and their size continued to increase up to 6 days after radiolabelled antibody injection. Tumor shrinking was then observed lasting for 4-12 weeks. In a control group injected with 600 microCi of 131I coupled to irrelevant monoclonal IgG, tumor growth was delayed, but no regression was observed. Tumors of mice injected with the corresponding amount of unlabelled antibodies grew like those of untreated mice. Based on measurements of the effective whole-body half-life of injected 131I, the mean radiation dose received by the animals was calculated to be 382 rads for the antibody group and 478 rads for the normal IgG controls. The genetically immunodeficient animals exhibited no increase in mortality, and only limited bone-marrow toxicity was observed. Direct measurement of radioactivity in mice dissected 1, 3 and 7 days after 131I-MAb injection showed that 25, 7.2 and 2.2% of injected dose were recovered per gram of tumor, the mean radiation dose delivered to the tumor being thus more than 5,000 rads. These experiments show that therapeutic doses of radioactivity can be selectively directed to human colon carcinoma by i.v. injection of 131I-labelled anti-CEA MAbs.
Buchegger
F
F
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Vacca
A
A
Carrel
S
S
Schreyer
M
M
Mach
J P
JP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000302:isolation & purification; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes