Therapeutic efficacy of a high-affinity anticarcinoembryonic antigen monoclonal antibody (COL-1).
COL-1 is a murine IgG2a monoclonal antibody (MAb) with a high affinity (1.4 x 10(9) M-1) for carcinoembryonic antigen (CEA) and no detectable reactivity for CEA-related antigens, such as nonspecific cross-reacting antigen (NCA) and normal fecal antigen (NFA). 125I-labeled COL-1 IgG was shown to efficiently and specifically target the LS-174T human colon carcinoma xenograft in athymic mice. Dose titration studies in this same model with 131I-labeled COL-1 demonstrated reduction of tumor growth rate when 300 microCi of the immunoconjugate was used (0.005 > p > 0.001). Administration of higher levels as a single dose led to increased toxicity. Dose fractionation experiments with 131I-COL-1 demonstrated the ability to administer much higher levels of the immunoconjugate with little or no toxicity, which resulted in a greater therapeutic efficacy. For example, three fractions of 200 microCi of 131I-COL-1 given at weekly intervals (for a total of 600 microCi) resulted in the substantial reduction (p < 0.0005) of the growth of established tumors in 100% (7/7) of mice, and in no evidence of tumor growth in 71% (5/7) of mice, at the end of the 63-day observation period. These results thus demonstrate the potential therapeutic efficacy for radiolabeled COL-1 in clinical trials and demonstrate the principle of the advantage of dose fractionation protocols for this immunoconjugate.
Siler
K
K
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, Maryland.
Eggensperger
D
D
Hand
P H
PH
Milenic
D E
DE
Miller
L S
LS
Houchens
D P
DP
Hinkle
G
G
Schlom
J
J
D002288:Adenocarcinoma, Mucinous / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes