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

Jingtao Chen, Gerard Zurawski, Sandy Zurawski, Zhiqing Wang, Keiko Akagawa, SangKon Oh, Ueno Hideki, Joseph Fay, Jacques Banchereau, Wenru Song, A. Karolina Palucka

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Article number35
JournalJournal of Hematology and Oncology
Volume8
Issue number1
DOIs
StatePublished - Dec 12 2015
Externally publishedYes

    Fingerprint

Keywords

  • Cyclin D1
  • Dendritic cells
  • Mantle cell lymphoma
  • Tumor antigen
  • Vaccine

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Chen, J., Zurawski, G., Zurawski, S., Wang, Z., Akagawa, K., Oh, S., Hideki, U., Fay, J., Banchereau, J., Song, W., & Palucka, A. K. (2015). A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40 Hematology & Oncology. Journal of Hematology and Oncology, 8(1), [35]. https://doi.org/10.1186/s13045-015-0131-7