title: Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients.
abstract: Tumor-specific clonal immunoglobulin expressed by B-cell lymphomas (idiotype [Id]) can serve as a target for active immunotherapy. We have previously described the vaccination of 4 patients with follicular lymphoma using dendritic cells (DCs) pulsed with tumor-derived Id protein and now report on 35 patients treated using this approach. Among 10 initial patients with measurable lymphoma, 8 mounted T-cell proliferative anti-Id responses, and 4 had clinical responses--2 complete responses (CRs) (progression-free [PF] for 44 and 57 months after vaccination), 1 partial response (PR) (PF for 12 months), and 1 molecular response (PF for 75+ months). Subsequently, 25 additional patients were vaccinated after first chemotherapy, and 15 of 23 (65%) who completed the vaccination schedule mounted T-cell or humoral anti-Id responses. Induction of high-titer immunoglobulin G anti-Id antibodies required coupling of Id to the immunogenic carrier protein keyhole limpet hemocyanin (Id-KLH). These antibodies could bind to and induce tyrosine phosphorylation in autologous tumor cells. Among 18 patients with residual tumor at the time of vaccination, 4 (22%) had tumor regression, and 16 of 23 patients (70%) remain without tumor progression at a median of 43 months after chemotherapy. Six patients with disease progression after primary DC vaccination received booster injections of Id-KLH protein, and tumor regression was observed in 3 of them (2 CRs and 1 PR). We conclude that Id-pulsed DC vaccination can induce T-cell and humoral anti-Id immune responses and durable tumor regression. Subsequent boosting with Id-KLH can lead to tumor regression despite apparent resistance to the primary DC vaccine.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, CA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Timmerman
authors.forename: Debra K
authors.initials: DK
authors.lastname: Czerwinski
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Hsu
authors.forename: Claudia
authors.initials: C
authors.lastname: Benike
authors.forename: Zheng Mei
authors.initials: ZM
authors.lastname: Hao
authors.forename: Behnaz
authors.initials: B
authors.lastname: Taidi
authors.forename: Ranjani
authors.initials: R
authors.lastname: Rajapaksa
authors.forename: Clemens B
authors.initials: CB
authors.lastname: Caspar
authors.forename: Craig Y
authors.initials: CY
authors.lastname: Okada
authors.forename: Adrienne
authors.initials: A
authors.lastname: van Beckhoven
authors.forename: Tina Marie
authors.initials: TM
authors.lastname: Liles
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005500:Follow-Up Studies; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology* / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D007130:Immunoglobulin Idiotypes; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin