A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma
<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it&...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-01-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/8/1/8 |
| _version_ | 1818834345289318400 |
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| author | Steinberg Seth M Linehan W Marston Herrin Vincent E Gause Barry Toubaji Antoun Ibrahim Ramy Ashtar Ed Rahma Osama E Grollman Frank Grimes George Bernstein Sarah A Berzofsky Jay A Khleif Samir N |
| author_facet | Steinberg Seth M Linehan W Marston Herrin Vincent E Gause Barry Toubaji Antoun Ibrahim Ramy Ashtar Ed Rahma Osama E Grollman Frank Grimes George Bernstein Sarah A Berzofsky Jay A Khleif Samir N |
| author_sort | Steinberg Seth M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p> |
| first_indexed | 2024-12-19T02:33:20Z |
| format | Article |
| id | doaj.art-8b7a709187b04833bad111199411db06 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-19T02:33:20Z |
| publishDate | 2010-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-8b7a709187b04833bad111199411db062022-12-21T20:39:33ZengBMCJournal of Translational Medicine1479-58762010-01-0181810.1186/1479-5876-8-8A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell CarcinomaSteinberg Seth MLinehan W MarstonHerrin Vincent EGause BarryToubaji AntounIbrahim RamyAshtar EdRahma Osama EGrollman FrankGrimes GeorgeBernstein Sarah ABerzofsky Jay AKhleif Samir N<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p>http://www.translational-medicine.com/content/8/1/8 |
| spellingShingle | Steinberg Seth M Linehan W Marston Herrin Vincent E Gause Barry Toubaji Antoun Ibrahim Ramy Ashtar Ed Rahma Osama E Grollman Frank Grimes George Bernstein Sarah A Berzofsky Jay A Khleif Samir N A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma Journal of Translational Medicine |
| title | A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma |
| title_full | A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma |
| title_fullStr | A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma |
| title_full_unstemmed | A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma |
| title_short | A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma |
| title_sort | pilot clinical trial testing mutant von hippel lindau peptide as a novel immune therapy in metastatic renal cell carcinoma |
| url | http://www.translational-medicine.com/content/8/1/8 |
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