Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

The level of mhc class i expression on murine adenocarcinoma can change the antitumor effector mechanism of immunocytokine therapy

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Imboden, M.
  • Murphy, K. R.
  • Rakhmilevich, A. L.
  • Neal, Z. C.
  • Xiang, R.
  • Reisfeld, Ralph
  • Gillies, S. D.
  • Sondel, P. M.

publication date

  • February 2001

journal

  • Cancer Research  Journal

abstract

  • The huKS1/4-IL2 fusion protein, directed against the human epithelial cell adhesion molecule (huEpCAM) has been shown to induce a strong CD8+ T-cell-dependent, natural killer (NK) cell-independent, antitumor response in mice bearing the huEp-CAM-transfected CT26 colon cancer CT26-EpCAM. Here we investigate the effectiveness of huKS1/4-IL2 against CT26-Ep21.6, a subclone of CT26-EpCAM, expressing low levels of MHC class I. In vitro antibody-dependent cellular cytotoxicity (ADCC) assays in the presence of huKS1/4-IL2 demonstrate that murine NK cells from spleen and blood can kill CT26-Ep21.6 significantly better than they kill CT26-EpCAM. NK-mediated ADCC of CT26-EpCAM can be enhanced by blocking the murine NK cell-inhibitory receptor, Ly-49C. A potent in vivo antitumor effect was observed when BALB/c mice bearing experimental metastases of CT26-Ep21.6 were treated with huKS1/4-IL2. The depletion of NK cells during huKS1/4-IL2 treatment significantly reduced the antitumor effect against CT26-Ep21.6. Together our in vitro and in vivo data in the huEp-CAM-transfected CT26 models indicate that the amount of MHC class I expressed on the tumor target cell plays a critical role in the in vivo antitumor mechanism of huKS1/4-IL2 immunotherapy. A low MHC class I level favors NK cells as effectors, whereas a high level of MHC class I favors T cells as effectors. Given the heterogeneity of MHC class I expression seen in human tumors and the prevailing T-cell suppression in many cancer patients, the observation that huKS1/4-IL2 has the potential to effectively activate an NK cell-based antitumor response may be of potential clinical relevance.

subject areas

  • Adenocarcinoma
  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antibody-Dependent Cell Cytotoxicity
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Dose-Response Relationship, Immunologic
  • Female
  • H-2 Antigens
  • Immunoconjugates
  • Immunotherapy
  • Interleukin-2
  • Killer Cells, Natural
  • Lung Neoplasms
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Fusion Proteins
  • Spleen
  • Tumor Cells, Cultured
  • Up-Regulation
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0008-5472

PubMed ID

  • 11245457
scroll to property group menus

Additional Document Info

start page

  • 1500

end page

  • 1507

volume

  • 61

issue

  • 4

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support