Comparison of Therapeutic Efficacy and Host Toxicity of Two Different 131I-labelled Antibodies and Their Fragments in the GW-39 Colonic Cancer Xenograft Model

Int J Cancer. 1989 Aug 15;44(2):292-300. doi: 10.1002/ijc.2910440218.

Abstract

The in vivo uptake, therapeutic potential, and host toxicity were evaluated for both the intact IgG and F(ab')2 fragment of 2 murine monoclonal antibodies (MAbs) directed against either carcino-embryonic antigen (CEA), called NP-4, or colon-specific antigen-p (CSAp), called Mu-9, in the GW-39 human colorectal carcinoma grown in the hamster cheek pouch. Mu-9 IgG and F(ab')2 were retained longer by the tumor than was the NP-4 IgG or F(ab')2, respectively. Localization of the two antibodies by micro-autoradiography revealed two distinct patterns. Mu-9 was seen densely around whole acini of tumor cells, whereas NP-4 was found around each individual cell, albeit less densely. The anti-tumor effects of 131I-labelled Mu-9 and NP-4 IgG were equal, but the therapeutic effectiveness of Mu-9 F(ab')2 was significantly higher than NP-4 F(ab')2, as measured by change in tumor size. A dose-dependent increase in host toxicity, as measured by change in body weight and change in peripheral white blood cells (p-WBCs), was observed with 0.5 to 3.0 mCi doses of 131I-IgG regardless of the MAb used. A 10-22% loss in body weight lasting 3-7 weeks and a 50-80% loss in pWBCs lasting 6-8 weeks were observed in these animals. In contrast, 3 x 2 mCi doses of 131I-NP-4 or Mu-9 F(ab')2 given at 3-day intervals, a schedule which was equally therapeutic to a single 2-mCi dose of 131I-IgG, resulted in only a 9% loss in body weight and a 50% loss in pWBCs that lasted only 1 week. This was followed by a complete recovery over the next 2-3 weeks. These data suggest that multiple doses of F(ab')2 can be as tumoricidal as a single dose of an intact MAb IgG, but significantly less toxic to the host.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal / toxicity
  • Antibody Formation
  • Antigens, Neoplasm / immunology
  • Carcinoembryonic Antigen / immunology
  • Colonic Neoplasms / therapy*
  • Cricetinae
  • Female
  • Humans
  • Immunoglobulin Fab Fragments / immunology*
  • Immunoglobulin G / immunology*
  • Iodine Radioisotopes / administration & dosage*
  • Iodine Radioisotopes / therapeutic use
  • Leukocyte Count
  • Mesocricetus
  • Neoplasm Transplantation
  • Transplantation, Heterologous

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Carcinoembryonic Antigen
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Iodine Radioisotopes
  • colon-specific antigen