Phase I/II study of immunotherapy using autologous tumor lysate-pulsed dendritic cells in patients with metastatic renal cell carcinoma

Autor: Hyun Moo Lee, Soyoung Baek, Hyounmie Doh, Chul Won Jung, Yong-Soo Bae, Chae Young Kim, Keunchil Park, Han Yong Choi, Byong-Moon Kim, Kihyun Kim, Won Ki Kang, Hyunah Lee, Won Seog Kim, Yoon Lee, Choon-Ju Jeon, Ho Yeong Im, Jung Han Kim
Rok vydání: 2007
Předmět:
Zdroj: Clinical Immunology. 125:257-267
ISSN: 1521-6616
DOI: 10.1016/j.clim.2007.07.014
Popis: This phase I/II study was conducted to evaluate the feasibility, safety and efficacy of immunotherapy using tumor lysate (TL)-pulsed dendritic cells (DC) in patients with metastatic renal cell carcinoma (RCC). DC were generated by culturing peripheral blood mononuclear cells in the presence of GM-CSF and IL-4 and were pulsed with autologous TL and keyhole limpet hemocyanin (KLH). Maturation of DC was induced by a combined treatment of CD40 ligand, IFN and monocyte-conditioned medium. The patients were administered two cycles of TL-pulsed DCs vaccination, each of which comprised of four doses injected subcutaneously at biweekly intervals. Nine patients were included. The immunotherapy was well tolerated without severe side effects. One patient achieved an objective partial response (PR). Five patients showed stable disease (SD), and the remaining three had progressive disease (PD). With a median follow-up of 17.5 months, the median time to progression was 5.2 months and the median overall survival was 29 months. In the antigen-specific lymphocyte proliferation assay, eight patients showed a proliferative response, which tended to be stronger in patients with SD or PR than in patients with PD. The ELISPOT assay was performed in two patients and indicated that one patient with PR showed a much stronger response than another with PD. Our results suggest that TL-pulsed DC immunotherapy in combination with nephrectomy affect the natural course of RCC and are associated with clinical benefits for patients with metastatic diseases.
Databáze: OpenAIRE