title: Clinical and immunologic effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a therapy in metastatic renal cell carcinoma patients.
abstract: OBJECTIVE
  To evaluate the clinical and immunologic outcomes of DC (dendritic cell) vaccine with interleukin (IL)-2 and IFN-alpha 2a in metastatic renal cell carcinoma patients.
  
  
  METHODS
  Eighteen consented and eligible patients were treated. Peripheral blood monocytes were cultured ex vivo into mature DCs and loaded with autologous tumor lysate. Treatment consisted of five cycles of intranodal vaccination of DCs (1 x 10(7) cells/1 mL Lactated Ringer's solution), 5-day continuous i.v. infusion of IL-2 (18MiU/m2), and three s.c. injections of IFN-alpha 2a (6MiU) every other day. Response Evaluation Criteria in Solid Tumors criteria were used for disease assessment. Correlative immunologic end points included peripheral blood lymphocyte cell phenotype and function as well as peripheral blood anti-renal cell carcinoma antibody and cytokine levels.
  
  
  RESULTS
  All patients received between two and five treatment cycles. Toxicities consisted of known and expected cytokine side effects. Overall objective clinical response rate was 50% with three complete responses. Median time to progression for all patients was 8 months, and median survival has not been reached (median follow up of 37+ months). Treatment-related changes in correlative immunologic end points were noted and the level of circulating CD4(+) T regulatory cells had a strong association with outcome. Pre-IP-10 serum levels approached significance for predicting outcome.
  
  
  CONCLUSIONS
  The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted.
authors.affiliation: Medical Oncology Immunotherapy Group, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwaab
authors.forename: Adrian
authors.initials: A
authors.lastname: Schwarzer
authors.forename: Benita
authors.initials: B
authors.lastname: Wolf
authors.forename: Todd S
authors.initials: TS
authors.lastname: Crocenzi
authors.forename: John D
authors.initials: JD
authors.lastname: Seigne
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Crosby
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Jill C
authors.initials: JC
authors.lastname: Uhlenhake
authors.forename: Diane
authors.initials: D
authors.lastname: Mellinger
authors.forename: Cathy
authors.initials: C
authors.lastname: Foster
authors.forename: Zbigniew M
authors.initials: ZM
authors.lastname: Szczepiorkowski
authors.forename: Susan M
authors.initials: SM
authors.lastname: Webber
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Robert D
authors.initials: RD
authors.lastname: Harris
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barth
authors.forename: John A
authors.initials: JA
authors.lastname: Heaney
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D054357:Chemokine CXCL10 / Q000097:blood; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C114753:CXCL10 protein, human; D019496:Cancer Vaccines; D054357:Chemokine CXCL10; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; C082598:aldesleukin