Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer: a clinical phase I/II study

Item Type:	Article
Title:	Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer: a clinical phase I/II study
Creators Name:	Flörcken, A. and Kopp, J. and van Lessen, A. and Movassaghi, K. and Takvorian, A. and Jöhrens, K. and Möbs, M. and Schönemann, C. and Sawitzki, B. and Egerer, K. and Dörken, B. and Pezzutto, A. and Westermann, J.
Abstract:	Multi-kinase inhibitors have been established for the treatment of advanced renal cell cancer (RCC), but long-term results are still disappointing and immunotherapeutic approaches remain an interesting experimental option particularly in patients with a low tumor burden. DC are crucial for antigen-specific MHC-restricted T cell immunity. Furthermore, allogeneic HLA-molecules pose a strong immunogenic signal and may help to induce tumor-specific T cell responses. In this phase I/II trial, 7 patients with histologically confirmed progressive metastatic RCC were immunized repetitively with 1 × 10 ( 7) allogeneic partially HLA-matched DC pulsed with autologous tumor lysate following a schedule of 8 vaccinations over 20 weeks. Patients also received 3 Mio IE IL-2 sec.c. once daily starting in week 4. Primary endpoints of the study were feasibility and safety. Secondary endpoints were immunological and clinical responses. Vaccination was feasible and safe with no severe toxicity being observed. No objective response could be documented. However, while all patients had documented progress at study entry, 29% of the patients showed SD throughout the study with a mean TTP of 24.6 weeks (range 5 to 96 weeks). In 3/7 patients, TH1-polarized immune responses against RCC-associated antigens were observed. In one patient showing a minimal clinical response and a TTP of 96 weeks, clonally proliferated T cells against yet undefined antigens were induced by the vaccine. Vaccination with tumor antigen loaded DC remains an interesting experimental approach, but should rather be applied in the situation of minimal residual disease after systemic therapy. Additional depletion of regulatory cells might be a promising strategy.
Keywords:	Dendritic Cells, Tumor Vaccination, Renal Cell Cancer, Immune Response, T Cell Response
Source:	Human Vaccines & Immunotherapeutics
ISSN:	2164-5515
Publisher:	Landes Bioscience
Volume:	9
Number:	7
Page Range:	1217-1227
Date:	1 June 2013
Official Publication:	https://doi.org/10.4161/hv.24149
PubMed:	View item in PubMed

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