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Related Experiment Videos

The biologic window for chimeric L6 radioimmunotherapy

S J DeNardo1, G R Mirick, L A Kroger

  • 1University of California, Davis Medical Center, Sacramento.

Cancer
|February 1, 1994
PubMed
Summary
This summary is machine-generated.

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Radioimmunotherapy using 131I chimeric-L6 monoclonal antibody (MoAb) showed promise in advanced breast cancer. Increased interleukin-2 receptor levels correlated with higher tumor response, suggesting a synergistic effect of radiation and immune activation.

Area of Science:

  • Oncology
  • Immunotherapy
  • Radiopharmaceuticals

Background:

  • Radioimmunotherapy (RIT) for adenocarcinoma has faced challenges due to low tumor uptake of monoclonal antibodies (MoAb).
  • Previous studies showed therapeutic response with 131I chimeric-L6 MoAb in advanced cancers.
  • L6 MoAb targets a specific antigen present in various human carcinomas, including breast cancer.

Purpose of the Study:

  • To evaluate the efficacy and biological effects of 131I chimeric-L6 MoAb radioimmunotherapy in patients with metastatic breast cancer.
  • To investigate the relationship between MoAb dose, vascular permeability, and therapeutic response.
  • To assess the role of serum cytokines and complement activation in RIT response.

Main Methods:

  • Nine patients with metastatic breast cancer received 131I chimeric-L6 MoAb on two sequential days at 4-week intervals.

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  • Monitoring included serum cytokines, complement levels, albumin, MoAb blood clearance, and peripheral blood mononuclear cell activation.
  • Tumor uptake and response to therapy were documented.

    • Main Results:

    • Infusion of L6 or chimeric-L6 MoAb led to immediate serum-complement activation.
    • Higher tumor uptake of the second 131I MoAb dose was observed after repeated MoAb administration.
    • Elevated soluble interleukin-2 receptor (IL-2R) levels, observed with higher MoAb doses (≥150 mg), correlated with improved therapeutic tumor response.

    Conclusions:

    • Measurable tumor regressions occurred in 5 out of 9 advanced metastatic breast cancer patients.
    • The observed therapeutic effects may result from increased radioimmunoconjugate delivery due to enhanced vascular permeability and synergistic effects of radiation and activated immune cells.
    • Targeting of pulmonary endothelium is unlikely to be the primary cause of observed biologic effects.