Design of CD40 agonists and their use in growing B cells for cancer immunotherapy

Richard S. Kornbluth, Mariusz Stempniak, Geoffrey W. Stone

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

CD40 stimulation has produced impressive results in early-stage clinical trials of patients with cancer. Further progress will be facilitated by a better understanding of how the CD40 receptor becomes activated and the subsequent functions of CD40-stimulated immune cells. This review focuses on two aspects of this subject. The first is the recent recognition that signaling by CD40 is initiated when the receptors are induced to cluster within the membrane of responding cells. This requirement for CD40 clustering explains the stimulatory effects of certain anti-CD40 antibodies and the activity of many-trimer, but not one-trimer, forms of CD40 ligand (CD40L, CD154). The second topic is the use of these CD40 activators to expand B cells ("CD40-B cells"). As antigen-presenting cells (APCs), CD40-B cells are as effective as dendritic cells, with the important difference that CD40 B cells can be induced to proliferate in vitro, whereas DCs proliferate poorly if at all. As a result, the use of CD40-B cells as antigen-presenting cells (APCs) promises to streamline the generation of anti-tumor CD8 + T cells for the adoptive cell therapy (ACT) of cancer.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalInternational reviews of immunology
Volume31
Issue number4
DOIs
StatePublished - Aug 1 2012

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Keywords

  • Acrp30
  • Adiponectin
  • Antibody therapy
  • B cell
  • Cancer
  • CD154
  • CD40
  • CD40L
  • Dendritic cell
  • FcgammaR
  • Multimer
  • Protein engineering
  • Receptor
  • Surfactant protein D
  • T cell
  • TNFSF5

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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