Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial

J Immunother. 2008 Oct;31(8):771-80. doi: 10.1097/CJI.0b013e3181833818.

Abstract

Therapeutic dendritic cell (DC) vaccination against cancer is a strategy aimed at activating the immune system to recognize and destroy tumor cells. In this nonrandomized phase 1/2 trial, we investigated the safety, feasibility, induction of T-cell response, and clinical response after treatment with a DC-based vaccine in patients with metastatic renal cell carcinoma. Twenty-seven patients with progressive cytokine-refractory metastatic renal cell carcinoma were vaccinated with DCs loaded with either a cocktail of survivin and telomerase peptides or tumor lysate depending on their HLA-A2 haplotype, and low-dose IL-2 was administered concomitantly. Tumor response, immune response, and serum IL-6 and YKL-40 were measured during treatment. Vaccine generation was successful in all patients and no serious adverse events were observed. None of the patients had an objective response but 13/27 patients obtained disease stabilization (SD) for more than 8 weeks. An antigen-specific immune response was demonstrated in 6/6 patients tested. Furthermore, significant alterations in serum YKL-40 and IL-6 were found during treatment. In conclusion, DC vaccination in our setting is feasible and without severe toxicity. Almost half of the patients obtained SD, and in more than 1/3 of the patients, SD persisted for more than 6 months. However, the evaluation of SD is difficult to interpret in the absence of a randomized trial and, therefore, these results should be interpreted with caution. Antigen-specific immune responses were observed in a subset of the treated patients.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Adult
  • Aged
  • Amino Acid Sequence
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Renal Cell / secondary
  • Carcinoma, Renal Cell / therapy*
  • Cell Line, Tumor
  • Chitinase-3-Like Protein 1
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Glycoproteins / blood
  • Humans
  • Immunotherapy, Adoptive*
  • Inhibitor of Apoptosis Proteins
  • Interleukin-2 / immunology
  • Interleukin-2 / therapeutic use
  • Interleukin-6 / blood
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy*
  • Lectins
  • Male
  • Microtubule-Associated Proteins / immunology
  • Middle Aged
  • Molecular Sequence Data
  • Peptides / immunology
  • Survivin
  • T-Lymphocytes, Cytotoxic / immunology
  • Telomerase / immunology
  • Vaccination

Substances

  • Adipokines
  • BIRC5 protein, human
  • CHI3L1 protein, human
  • Cancer Vaccines
  • Chitinase-3-Like Protein 1
  • Glycoproteins
  • Inhibitor of Apoptosis Proteins
  • Interleukin-2
  • Interleukin-6
  • Lectins
  • Microtubule-Associated Proteins
  • Peptides
  • Survivin
  • Telomerase