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Regression of human metastatic renal cell carcinoma after vaccination with tumor cell–dendritic cell hybrids

A Retraction to this article was published on 01 September 2003

Abstract

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's immune system in controlling the devastating course of metastatic renal cell carcinoma1,2,3. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models4,5,6,7,8. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques5, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a ‘mixed response’, and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

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Figure 1: Characterization of the hybrid cell vaccine.
Figure 2: Immunological response data.
Figure 3: Clinical response to hybrid cell vaccination.

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Acknowledgements

The authors thank M. Striepe. The general support of the blood bank, departments of radiology and radiotherapy and the HLA laboratory of the University of Göttingen is acknowledged.

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Correspondence to Gerhard A. Müller or Rolf-Hermann Ringert.

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Kugler, A., Stuhler, G., Walden, P. et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell–dendritic cell hybrids. Nat Med 6, 332–336 (2000). https://doi.org/10.1038/73193

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