A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40

J Hematol Oncol. 2015 Apr 14:8:35. doi: 10.1186/s13045-015-0131-7.

Abstract

Background: Mantle cell lymphoma (MCL) is a distinct clinical pathologic subtype of B cell non-Hodgkin's lymphoma often associated with poor prognosis. New therapeutic approaches based on boosting anti-tumor immunity are needed. MCL is associated with overexpression of cyclin D1 thus rendering this molecule an interesting target for immunotherapy.

Methods: We show here a novel strategy for the development of recombinant vaccines carrying cyclin D1 cancer antigens that can be targeted to dendritic cells (DCs) via CD40.

Results: Healthy individuals and MCL patients have a broad repertoire of cyclin D1-specific CD4(+) and CD8(+) T cells. Cyclin D1-specific T cells secrete IFN-γ. DCs loaded with whole tumor cells or with selected peptides can elicit cyclin D1-specific CD8(+) T cells that kill MCL tumor cells. We developed a recombinant vaccine based on targeting cyclin D1 antigen to human DCs via an anti-CD40 mAb. Targeting monocyte-derived human DCs in vitro with anti-CD40-cyclin D1 fusion protein expanded a broad repertoire of cyclin D1-specific CD4(+) and CD8(+) T cells.

Conclusions: This study demonstrated that cyclin D1 represents a good target for immunotherapy and targeting cyclin D1 to DCs provides a new strategy for mantle cell lymphoma vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD40 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology*
  • Cyclin D1 / immunology*
  • Dendritic Cells / immunology*
  • Humans
  • In Vitro Techniques
  • Lymphocyte Activation / immunology
  • Lymphoma, Mantle-Cell / immunology*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Recombinant Fusion Proteins / immunology
  • Vaccines, Synthetic / immunology

Substances

  • CCND1 protein, human
  • CD40 Antigens
  • Cancer Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Cyclin D1