Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response

Int Immunopharmacol. 2010 Aug;10(8):865-74. doi: 10.1016/j.intimp.2010.04.024. Epub 2010 May 16.

Abstract

Vaccination with neem leaf glycoprotein matured carcinoembryonic antigen (CEA) pulsed dendritic cells (DCs) enhances antigen-specific humoral and cellular immunity against CEA and restricts the growth of CEA(+) murine tumors. NLGP helps better CEA uptake, processing and presentation to T/B cells. This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells. In addition to T cell response, DCNLGPCEA vaccine generates anti-CEA antibody response, which is principally IgG2a in nature. This antibody participates in cytotoxicity of CEA(+) cells in antibody-dependent manner. This strong anti-CEA cellular and humoral immunity protects mice from tumor development and these mice remained tumor free following second tumor inoculation, indicating generation of effector memory response. Evaluation of underlying mechanism suggests vaccination generates strong CEA specific CTL and antibody response that can completely prevent the tumor growth following adoptive transfer. In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Animals
  • Antigen Presentation / drug effects
  • Azadirachta / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cancer Vaccines* / administration & dosage
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Cytotoxicity, Immunologic / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Immunologic Memory / drug effects
  • Lymphocyte Activation / drug effects
  • Mice
  • Neoplasm Transplantation
  • Plant Leaves
  • Plant Proteins / administration & dosage*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • DCNLGPCEA vaccine
  • Plant Proteins