Improved radioimmunotherapy of colorectal cancer xenografts using antibody mixtures against carcinoembryonic antigen and colon-specific antigen-p.
Radioimmunotherapy of GW-39 human colonic tumor xenografts grown in the hamster cheek pouch with 131I-labeled NP-4 anti-(carcinoembryonic antigen) (CEA) and 131I-labeled Mu-9 anti-(color-specific antigen-p) (CSAp) murine monoclonal antibodies, administered in combination, was more effective than using either antibody alone for tumor masses less than 0.5 cm3 in size. The antibody mixture had no therapeutic advantage for larger tumors. Therapeutic efficacy was determined by measuring the change in tumor size over time, quantifying the absolute number of tumors responding to radioantibody therapy, and determining the percentage growth inhibition of each treatment at various times after radioantibody administration. Several mechanisms are discussed to explain the improved tumoricidal effect of the antibody mixture noted in this model system, such as (a) the possibility that an antibody mixture could target a greater number of tumor cells, (b) the potential for antibody mixtures to provide better tumor distribution and (c) the possibility that antibodies administered in combination can increase the magnitude of tumor uptake of individual radioantibodies, thereby resulting in a greater radiation dose delivered to the tumor.
Blumenthal
R D
RD
Center for Molecular Medicine and Immunology, Neward, N.J. 07103.
Kashi
R
R
Stephens
R
R
Sharkey
R M
RM
Goldenberg
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002455:Cell Division / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D006224:Cricetinae; D005260:Female; D007167:Immunotherapy; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008647:Mesocricetus; D009368:Neoplasm Transplantation; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; C030139:colon-specific antigen