title: Development of a dendritic cell-based vaccine for chronic lymphocytic leukemia.
abstract: Evidence for the existence of CLL-specific antigens recognized by the immune system can be gathered from the observation that many patients display monoclonal or oligoclonal expansions and skewed repertoire of T cells. In vitro functional studies have shown that tumor-specific T-cells are able to lyse the leukemic cells. Antileukemic cellular immunity may be boosted in vivo using dendritic cell-based immunotherapy. Our preclinical studies provide evidence that DC that had endocytosed apoptotic CLL cells (Apo-DC) were superior to fusion hybrids, tumor lysate or RNA in eliciting antileukemic T-cell responses in vitro. We have validated a method for enriching the small number of monocyte precursors present in the peripheral blood of CLL patients and utilize them for generating individualized, Apo-DC cellular vaccines. In most cases, a minimum of 50 x 10(6) Apo-DC could be generated, beginning with immunomagnetically enriched monocytes from a single leukapheresis product containing at least 1% CD14+ cells. Cryopreservation and thawing did not affect the phenotype or the T cell stimulatory function of Apo-DC. A phase I/II, open label clinical trial examining the feasibility, safety and immunogenicity of Apo-DC vaccination has been initiated. CLL patients receive 10(7) Apo-DC for at least five immunizations and monitored clinically and immunologically for 52 weeks. Three cohorts are accrued stepwise. Cohort I receives Apo-DC alone; Cohort II: Apo-DC+ repeated doses of low-dose GM-CSF; Cohort III: low-dose cyclophosphamide followed by Apo-DC + GM-CSF.
authors.affiliation: Departments of Oncology and Hematology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Palma
authors.forename: L
authors.initials: L
authors.lastname: Adamson
authors.forename: L
authors.initials: L
authors.lastname: Hansson
authors.forename: P
authors.initials: P
authors.lastname: Kokhaei
authors.forename: R
authors.initials: R
authors.lastname: Rezvany
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.forename: A
authors.initials: A
authors.lastname: Osterborg
authors.forename: A
authors.initials: A
authors.lastname: Choudhury
mesh_terms: D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines