title: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells.
abstract: OBJECTIVE
  We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC).
  
  
  METHODS
  Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, and prostaglandin E2.
  
  
  RESULTS
  Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive.
  
  
  CONCLUSIONS
  Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.
authors.affiliation: Department of Urology, University of Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Höltl
authors.forename: Claudia
authors.initials: C
authors.lastname: Zelle-Rieser
authors.forename: Hubert
authors.initials: H
authors.lastname: Gander
authors.forename: Christine
authors.initials: C
authors.lastname: Papesh
authors.forename: Reinhold
authors.initials: R
authors.lastname: Ramoner
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Hermann
authors.initials: H
authors.lastname: Rogatsch
authors.forename: Adel L
authors.initials: AL
authors.lastname: Barsoum
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Coggin
authors.forename: Martin
authors.initials: M
authors.lastname: Thurnher
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006433:Hemocyanins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007167:Immunotherapy; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007680:Kidney Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D015232:Dinoprostone; D006433:Hemocyanins; D007136:Immunoglobulins; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C032808:keyhole-limpet hemocyanin