Fused Cell Vacccine Abstracts and References
Dendritic Cell Vaccine Abstracts
Regression of human metastatic renal cell carcinoma after vaccination with tumor cell–dendritic cell hybrids. Nature Medicine March 2000 Volume 6 Number 3 pp 332-336
Alexander Kugler1, 7, Gernot Stuhler2, 7, Peter Walden3, Gerhard Zöller1, Anke Zobywalski2, Peter Brossart2, Uwe Trefzer3, Silke Ullrich1, Claudia A. Müller4, Volker Becker5, Andreas J. Gross1, Bernhard Hemmerlein6, Lothar Kanz2, Gerhard A. Müller5& Rolf-Hermann Ringert1
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 carcinoma1-3. 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 models4-8. 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.
Author Affiliations and Contact Info
1. Department of Urology, University of Göttingen , Germany
2. Department II, Medical University Clinic, Tübingen, Germany
3. Department of Dermatology, Charité, Humboldt University, Berlin, Germany
4. Section of Transplantation Immunology and Immunohaematology, Department II, Medical University Clinic, Tübingen, Germany
5. Department of Nephrology and Rheumatology, University of Göttingen, Germany
6. Department of Pathology, University of Göttingen , Germany
7. A.K. and G.S. contributed equally to this study. Correspondence should be addressed to G A Müller. e-mail: [email protected] and R -H Ringert. e-mail: [email protected]
See also this helpful commentary on the above article:
Kufe, DW Smallpox, Polio and now a cancer Vaccine? Nature Medicine March 2000, Volume 6 Number 3 PP252-253
B-Cell Vaccine Abstracts
American Society of of Nephrology 1998 Annual Meeting (Oct 1998) S510: HYBRID-CELL-VACCINATION IS A NEW APPROACH IN THE TREATMENT OF METASTATIC RENAL CELL CARCINOMA (RCC)
G.A. Muller,1* V. Becker,1* A. Kugler,2* B. Berner,1* F. Strutz,1 B. Raschke,1* C.A. Muller,3* F. Seseke,2* M. Kallerhoff,2* P. Thelen,2* W. Fenner,4* W.Schott,4* R.H. Ringert.2*
The median time of survival for patients with renal cell carcinoma (RCC) is 12 to 18 months after metastasis for this cancer usually fails to respond to chemotherapy and other therapeutic regimens such as treatment with interleukines or interferrons. However, spontaneous remissions were reported in 1 to 7 % of cases pointing to some immune mediated mechanisms, although a specific tumor antigen has not been identified so far. For this reason, we have chosen a therapy regimen stimulating the immune system by resembling graft rejection disease after transplantation of foreign HLA-antigens. We treated 32 patients with progressive metastatic RCC in a phase I/II study with a hybrid cell vaccine to stimulate tumor specific immune responses. This vaccine was generated according to GPC criteria by electrofusion of either autologous or allogeneic tumor cells with pooled activated allogeneic B-lymphocytes. The B-lymphocytes were obtained from healthy volunteers who had different HLA-A, -B, -C antigens compared with the recipients. The fusion product was lethally irradiated and applied to the patiens by multiple subcutaneous injections. Boostering was performed up to 6 times in 3 months intervals. The mean follow-up was 7.5 months (1-30 months). 4 out of 32 patients (12,5 %) showed a complete response with full regression of their metastases and another 3 patients showed an initial partial response. In 7 patients progressive disease was stabilized for several months. No side effects except mild fever for one day in 5 patients were observed. Seven patients who responded to this vaccination showed a positive DTH reaction when tumor cells were subcutaneously reinjected on day 10 after treatment. Moreover, immunohistological analysis of biopsies from the injection side showed infiltration of CD8+ and CD4+ T-cells as a further sign of stimulation of immune reactions against malignant cells. Thus active specific immunotherapy seems to be a promising new approach in the treatment of metastatic RCC. A multicenter study will now be conducted.
Author Affiliations and Contact Info
1. Dept. of Nephrology & Rheumatology, University of Gottingen
2. Dept. of Urology, University of Gottingen
3. Section of Transplantation-Immunology and Immunhematology, University
4. Dept. of Urology, NZN Hann. Munchen.
Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma. Br J Urol 1998 Oct;82(4):487-93
Kugler A, Seseke F, Thelen P, Kallerhoff M, Muller GA, Stuhler G, Muller C, Ringert RH
Department of Urology, University of Gottingen, Germany.
OBJECTIVE: To evaluate the safety, acute and long-term toxicity and therapeutic activity of an allogenic and an autologous hybrid cell vaccine in patients with progressive metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients were vaccinated with a lethally irradiated hybrid cell vaccine of allogenic RCC tumour cells fused with major histocompatibility complex class I-matched and class II-unmatched activated allogenic lymphocytes. These patients were then followed for a mean of 11 months. Another 13 patients were vaccinated with a hybrid cell vaccine of autologous tumour cells fused with allogenic activated lymphocytes and followed for a mean of 6 months. RESULTS: Six of the 11 patients receiving the allogenic vaccination showed an initial response, with two complete and two partial responses to date. Only three patients who received autologous vaccination responded to treatment. CONCLUSIONS: Hybrid cell vaccination is a promising new approach in the treatment of patients with advanced RCC.
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