title: A novel vaccine for mantle cell lymphoma based on targeting cyclin D1 to dendritic cells via CD40.
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.
authors.affiliation: Institute of Translational Medicine, the First Hospital, Jilin University, Changchun, 130031, China. jtchen@jlu.edu.cn.|Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. jtchen@jlu.edu.cn.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. gerardz@baylorhealth.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. sandyz@baylorhealth.edu.
authors.forename: Sandy
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. zhiqingw@baylorhealth.edu.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. rbg599@gmail.com.
authors.forename: Keiko
authors.initials: K
authors.lastname: Akagawa
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. sangkono@baylorhealth.edu.
authors.forename: Sangkon
authors.initials: S
authors.lastname: Oh
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. hidekiu@baylorhealth.edu.
authors.forename: Ueno
authors.initials: U
authors.lastname: Hideki
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. Joseph.Fay@baylorhealth.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fay
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. Jacque.Banchereau@jax.org.|The Present address: The Jackson Laboratory for Genomics Medicine, Farmington, CT, USA. Jacque.Banchereau@jax.org.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. wenru.song@gmail.com.|The Present address: AstraZeneca Pharmaceuticals LP, Gaithersburg, MD, USA. wenru.song@gmail.com.
authors.forename: Wenru
authors.initials: W
authors.lastname: Song
authors.affiliation: Baylor Institute for Immunology Research and Sammons Cancer Center, Dallas, TX, 75204, USA. Karolina.Palucka@jax.org.|The Present address: The Jackson Laboratory for Genomics Medicine, Farmington, CT, USA. Karolina.Palucka@jax.org.
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
mesh_terms: D000368:Aged; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D019938:Cyclin D1 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D020522:Lymphoma, Mantle-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C530104:CCND1 protein, human; D019013:CD40 Antigens; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D019938:Cyclin D1