You are here

  • Home
  • Archive
  • Volume 45, Issue 4
  • Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7

Article Text

Article menu
Download PDFPDF
Colorectal cancer
Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7
  1. C A Maxwell-Armstronga,
  2. L G Durranta,b,
  3. R A Robinsc,
  4. A M Galvinc,
  5. J H Scholefielda,
  6. J D Hardcastlea
  1. aUniversity Department of Surgery, Queen’s Medical Centre, Nottingham NG7 2UH, UK, bUniversity Department of Clinical Oncology, City Hospital, Nottingham NG5 1PB, UK, cDepartment of Immunology, University of Nottingham, Nottingham, UK
  1. Mr Maxwell-Armstrong.

Abstract

BACKGROUND The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed on 70–80% of colorectal cancers. Phase I studies have shown that the vaccine is non-toxic, and a number of patients have been immunised prior to resection of their primary tumours.

AIMS To assess lymphocyte activation at the tumour site by measuring expression of the α subunit of the interleukin 2 receptor (CD25).

METHODS Nineteen patients with primary colorectal cancer were immunised with varying doses of 105AD7 prior to resection of their primary tumours. Samples of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. Samples from a matched control group were also stained. Fresh tumours from 14 immunised patients and 31 unimmunised control patients were disaggregated, and the lymphocytes obtained labelled for CD25. Samples were analysed blindly by flow cytometry.

RESULTS Median infiltration of lymphocytes expressing CD25, measured immunohistochemically, was higher in trial patients, as was the ratio of tumour to normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unmatched controls.

DISCUSSION The α subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.

  • anti-idiotypic antibody
  • colorectal cancer
  • immunotherapy
  • 105AD7

  • Abbreviations used in this paper

    FCS
    fetal calf serum
    FITC
    fluorescein isothiocyanate
    IL-2
    interleukin 2
    IQR
    interquartile range
    MHC
    major histocompatibility complex
    NK
    natural killer
    PE
    phycoerythrin
    TAA
    tumour associated antigen
    TBS
    Tris buffered saline
    TIL
    tumour infiltrating lymphocytes

    • https://doi.org/10.1136/gut.45.4.593

    Statistics from Altmetric.com

      Request Permissions

      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    • Abbreviations used in this paper

      FCS
      fetal calf serum
      FITC
      fluorescein isothiocyanate
      IL-2
      interleukin 2
      IQR
      interquartile range
      MHC
      major histocompatibility complex
      NK
      natural killer
      PE
      phycoerythrin
      TAA
      tumour associated antigen
      TBS
      Tris buffered saline
      TIL
      tumour infiltrating lymphocytes
      • View Full Text