INVESTIGATIVE UROLOGY

Dendritic cell immunotherapy for urological cancers using cryopreserved allogeneic tumour lysate-pulsed cells: a phase I/II study
Pandha HS, John RJ, Hutchinson J, James N, Whelan M, Corbishley C, Dalgleish AG
Department of Histopathology, St George’s Hospital Medical School, Cranmer Terrace, London
BJU Int. 2004; 94: 412-8

• Objective: To assess the feasibility, toxicity and immunogenicity of dendritic cell (DC)-based immunotherapy in patients with advanced urological cancers.
• Patients and Methods: Patients with hormone-refractory prostate cancer (11) and metastatic renal cell carcinoma (five) received 1-3 x 10(6) intradermal allogeneic tumour lystate-pulsed DCs fortnightly for six vaccinations then monthly until disease progression. Intradermal keyhole limpet haemocyanin was injected near the DCs as the adjuvant. DC vaccine was prepared from buffy coats, then lysate-pulsed, cryopreserved in aliquots, and tested for phenotypic expression and activity in an allogeneic mixed lymphocyte reaction before clinical use.
• Results: There was no evidence of significant toxicity from vaccine or adjuvant. Delayed-type hypersensitivity skin testing and biopsy revealed a cellular infiltrate to intradermal re-challenge to tumour lysate and adjuvant in almost all patients. In addition, there was increased expression of T helper type 1 cytokines, interferon-gamma-expressing T cell by ELISPOT analysis, but also interleukin-10 in a few patients. Vaccination resulted in a reduction in the level of prostate-specific antigen (PSA) in one patient, a reduction in PSA velocity in a further man and an increased PSA doubling time in six. Two of five patients with renal cell carcinoma had stabilization of disease.
• Conclusion: The cryopreservation and repeated administration of DC vaccine was feasible and not toxic. There was evidence of induction of both humoral and cellular immunity to vaccine and adjuvant in most patients. The use of sequential aliquots of identical cryopreserved vaccine will ensure quality control and greatly facilitate future clinical studies in terms of consistency of vaccine administered and the provision of primed DCs for in vitro assessment of response.
  
  
• Editorial Comment
  This is a very well done scientific research with immediate potential clinical implications. As the authors stated, one of the most significant limitation to current dendritic cell-based immunotherapy is the need to prepare fresh vaccine repeatedly. The ability to culture and cryopreserve numerous aliquots of identical dendritic cells from a single venesection would reduce hospital intervention for patients, and greatly facilitate clinical trials by allowing the manipulation of dendritic cells before or after freezing, and their subsequent use as sequential vaccines.
  The authors demonstrated the feasibility of a potentially generic approach to cellular immunotherapy, and the preparation of identical aliquots of dendritic cell vaccine that were readily tested for safety and immunoreactivity before injecting into patients. Dendritic cell therapy resulted in significant in vitro immunological responses in patients even with very advanced disease. Also, in this study, dendritic cell vaccine showed to be safe and non-toxic

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil