Murine carcinoma expressing carcinoembryonic antigen-like protein is restricted by antibody against neem leaf glycoprotein

Immunol Lett. 2014 Nov;162(1 Pt A):132-9. doi: 10.1016/j.imlet.2014.08.004. Epub 2014 Aug 13.

Abstract

We have generated a polyclonal antibody against a novel immunomodulator, neem leaf glycoprotein (NLGP) that can react to a specific 47 kDa subunit of NLGP. Generated anti-NLGP antibody (primarily IgG2a) was tested for its anti-tumor activity in murine carcinoma (EC, CT-26), sarcoma (S180) and melanoma (B16Mel) tumor models. Surprisingly, tumor growth restriction was only observed in CT-26 carcinoma models, without any alteration in other tumor systems. Comparative examination of antigenicity between four different tumor models revealed high expression of CEA-like protein on the surface of CT-26 tumors. Subsequent examination of the cross-reactivity of anti-NLGP antibody with purified or cell bound CEA revealed prominent recognition of CEA by anti-NLGP antibody, as detected by ELISA, Western Blotting and immunohistochemistry. This recognition seems to be responsible for anti-tumor function of anti-NLGP antibody only on CEA-like protein expressing CT-26 tumor models, as confirmed by ADCC reaction in CEA(+) tumor systems where dependency to anti-NLGP antibody is equivalent to anti-CEA antibody. Obtained result with enormous therapeutic potential for CEA(+) tumors may be explained in view of the epitope spreading concept, however, further investigation is crucial.

Keywords: Antibody-dependent cellular cytotoxicity; CEA-like protein; Carcinoembryonic antigen; Colon cancer; Neem leaf glycoprotein; Polyclonal antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / immunology
  • Antibodies / pharmacology*
  • Antibody-Dependent Cell Cytotoxicity
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Azadirachta*
  • Carcinoembryonic Antigen / genetics*
  • Carcinoembryonic Antigen / immunology
  • Carcinoembryonic Antigen / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Carcinoma / immunology
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Melanoma, Experimental
  • Mice
  • Plant Leaves*
  • Plant Proteins / antagonists & inhibitors*
  • Plant Proteins / immunology
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies
  • Antineoplastic Agents
  • Carcinoembryonic Antigen
  • Glycoproteins
  • Immunoglobulin G
  • Plant Proteins