Preclinical evaluation of an anti-CD25 monoclonal antibody, 7G7/B6, armed with the beta-emitter, yttrium-90, as a radioimmunotherapeutic agent for treating lymphoma

Cancer Biother Radiopharm. 2009 Jun;24(3):303-9. doi: 10.1089/cbr.2008.0577.

Abstract

Objective: Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. We evaluated an anti-CD25 monoclonal Antibody, 7G7/B6, armed with (90)Y as a potential radioimmunotherapeutic agent for CD25-expressing lymphomas.

Materials and methods: The lymphoma model was established by subcutaneous injection of 1 x 10(7) SUDHL-1 cells into nude mice. The biodistribution of (111)In-7G7/B6 and therapeutic studies with (90)Y-7G7/B6 were performed in the tumor-bearing mice.

Results: Therapy using (90)Y-7G7/B6 prolonged survival of the SUDHL-1 lymphoma-bearing mice significantly, as compared with either untreated mice or the mice treated with (90)Y-11F11, a radiolabeled isotype-matched control antibody (p < 0.001). All of the mice in the control and the (90)Y-11F11 treatment groups died by days 18 and 24, respectively. In contrast, 30% of the mice in the low-dose group (75 microCi of (90)Y-7G7/B6/mouse) and 75% in the high-dose group (150 microCi of (90)Y-7G7/B6/mouse) became tumor free and remained healthy for greater than 6 months.

Conclusions: Our findings suggested that (90)Y-7G7/B6 is a potentially useful radioimmunotherapeutic agent for the treatment of patients with CD25-expressing lymphomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal / toxicity
  • Antibodies, Monoclonal, Humanized
  • Antibody Specificity / immunology
  • Cell Line, Tumor
  • Daclizumab
  • Disease-Free Survival
  • Endocytosis / immunology
  • Female
  • Humans
  • Immunoglobulin G / metabolism
  • Immunosuppressive Agents / metabolism
  • Interleukin-2 Receptor alpha Subunit / immunology*
  • Kaplan-Meier Estimate
  • Lymphoma / pathology
  • Lymphoma / radiotherapy*
  • Maximum Tolerated Dose
  • Mice
  • Mice, Nude
  • Radioimmunotherapy / methods*
  • Xenograft Model Antitumor Assays
  • Yttrium Radioisotopes / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Yttrium Radioisotopes
  • Daclizumab