Tumor regression induced by intratumor administration of adenovirus vector expressing CD40 ligand and naive dendritic cells. Academic Article uri icon

Overview

MeSH

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Antigens, CD40
  • CD4-Positive T-Lymphocytes
  • Cell Division
  • Colonic Neoplasms
  • Dose-Response Relationship, Immunologic
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Immunotherapy, Adoptive
  • Injections, Intralesional
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic

MeSH Major

  • CD40 Ligand
  • Dendritic Cells
  • Neoplasms, Experimental

abstract

  • We have previously shown that in vivo genetic modification of tumors with an adenovirus (Ad) vector engineered to express CD40 ligand (AdmCD40L) induces tumor-specific CTLs and suppresses tumor growth in vivo. In the present study, we investigate the hypothesis that this treatment can be made more efficient with 10(2)-fold less Ad vector by also administering bone marrow-generated dendritic cells (DCs) to the tumor. Using AdmCD40L and the number of DCs that alone had no effect on tumor growth, the data show that the growth of CT26 (colon adenocarcinoma; H-2d) and B16 (melanoma; H-2b) murine s.c. tumors is significantly suppressed by direct administration of DCs into s.c. established tumors that had been pretreated with AdmCD40L 2 days previously. The antitumor effect produced by the combination therapy AdmCD40L + DCs correlated with in vivo priming of tumor-specific CTLs. The antitumor cell-mediated immunity was transferable to naive mice by spleen cells from AdmCD40L + DC-treated animals. The interactions between CD40L and CD40 within treated tumors were critical because tumor suppression was abrogated by coadministration to the tumors of neutralizing monoclonal antibody against CD40L along with the DCs. Finally, in vivo depletion and knockout mice experiments demonstrated that tumor regression produced by this combination therapy depends on CD8+ T cells, but not on CD4+ T cells. These findings should be useful in designing strategies for use of DCs and AdmCD40L in cancer immunotherapy.

publication date

  • November 15, 2000

has subject area

  • Adenocarcinoma
  • Adenoviridae
  • Animals
  • Antigens, CD40
  • CD4-Positive T-Lymphocytes
  • CD40 Ligand
  • Cell Division
  • Colonic Neoplasms
  • Dendritic Cells
  • Dose-Response Relationship, Immunologic
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Immunotherapy, Adoptive
  • Injections, Intralesional
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Cytotoxic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 11103803

Additional Document Info

start page

  • 6391

end page

  • 6395

volume

  • 60

number

  • 22