Frontiers in Oncology (Feb 2019)
Safety and Therapeutic Profile of a GnRH-Based Vaccine Candidate Directed to Prostate Cancer. A 10-Year Follow-Up of Patients Vaccinated With Heberprovac
- Jesús A. Junco,
- Ranfis Rodríguez,
- Franklin Fuentes,
- Idania Baladrón,
- Maria D. Castro,
- Lesvia Calzada,
- Carmen Valenzuela,
- Eddy Bover,
- Eulogio Pimentel,
- Roberto Basulto,
- Niurka Arteaga,
- Angel Cid-Arregui,
- Francisco Sariol,
- Lourdes González,
- Liliana Porres-Fong,
- María Medina,
- Ayni Rodríguez,
- A. Hilda Garay,
- Osvaldo Reyes,
- Matilde López,
- Lourdes de Quesada,
- Allelin Alvarez,
- Carolina Martínez,
- Marleny Marrero,
- Guillermo Molero,
- Alfredo Guerra,
- Pedro Rosales,
- Carlos Capote,
- Sahily Acosta,
- Idania Vela,
- Lina Arzuaga,
- Ana Campal,
- Erlán Ruiz,
- Elier Rubio,
- Pável Cedeño,
- María Carmen Sánchez,
- Pedro Cardoso,
- Rolando Morán,
- Yairis Fernández,
- Magalys Campos,
- Henio Touduri,
- Dania Bacardi,
- Indalecio Feria,
- Amilcar Ramirez,
- Karelia Cosme,
- Pedro López Saura,
- Maricel Quintana,
- Verena Muzio,
- Ricardo Bringas,
- Marta Ayala,
- Mario Mendoza,
- Luis E. Fernández,
- Adriana Carr,
- Luis Herrera,
- Luis Herrera,
- Gerardo Guillén
Affiliations
- Jesús A. Junco
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Ranfis Rodríguez
- Uro-oncology Department of National Institute of Oncology and Radiobiology (INOR), Havana, Cuba
- Franklin Fuentes
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Idania Baladrón
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Maria D. Castro
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Lesvia Calzada
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Carmen Valenzuela
- Center for Molecular Immunology, Havana, Cuba
- Eddy Bover
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Eulogio Pimentel
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Roberto Basulto
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Niurka Arteaga
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Angel Cid-Arregui
- German Cancer Research Center, Heidelberg, Germany
- Francisco Sariol
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Lourdes González
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Liliana Porres-Fong
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- María Medina
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Ayni Rodríguez
- Department of Pharmacology of Camaguey Medical University, Camagüey, Cuba
- A. Hilda Garay
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Osvaldo Reyes
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Matilde López
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Lourdes de Quesada
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Allelin Alvarez
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Carolina Martínez
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Marleny Marrero
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Guillermo Molero
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Alfredo Guerra
- Department of Pharmacology of Camaguey Medical University, Camagüey, Cuba
- Pedro Rosales
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Carlos Capote
- Amalia Simoni Clinical-Surgical Hospital, Camagüey, Cuba
- Sahily Acosta
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Idania Vela
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Lina Arzuaga
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Ana Campal
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Erlán Ruiz
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Elier Rubio
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Pável Cedeño
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- María Carmen Sánchez
- Clinical Laboratory of the Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Pedro Cardoso
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Rolando Morán
- Center for Genetic Engineering and Biotechnology of Camaguey, Camagüey, Cuba
- Yairis Fernández
- Department of Pharmacology of Camaguey Medical University, Camagüey, Cuba
- Magalys Campos
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Henio Touduri
- Department of Pharmacology of Camaguey Medical University, Camagüey, Cuba
- Dania Bacardi
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Indalecio Feria
- 0Clinical Trials Department of Oncologic Hospital Marie Curie of Camaguey, Marie Curie, Camagüey, Cuba
- Amilcar Ramirez
- Department of Pharmacology of Camaguey Medical University, Camagüey, Cuba
- Karelia Cosme
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Pedro López Saura
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Maricel Quintana
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Verena Muzio
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Ricardo Bringas
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Marta Ayala
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Mario Mendoza
- Oncologic Hospital of Camaguey, Marie Curie, Camagüey, Cuba
- Luis E. Fernández
- Center for Molecular Immunology, Havana, Cuba
- Adriana Carr
- Center for Molecular Immunology, Havana, Cuba
- Luis Herrera
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- Luis Herrera
- 1BioCubafarma, Havana, Cuba
- Gerardo Guillén
- Center for Genetic Engineering and Biotechnology, Havana, Cuba
- DOI
- https://doi.org/10.3389/fonc.2019.00049
- Journal volume & issue
-
Vol. 9
Abstract
Heberprovac is a GnRH based vaccine candidate containing 2.4 mg of the GnRHm1-TT peptide as the main active principle; 245 μg of the very small size proteoliposomes adjuvant (VSSP); and 350 μL of Montanide ISA 51 VG oil adjuvant. The aim of this study was to assess the safety and tolerance of the Heberprovac in advanced prostate cancer patients as well as its capacity to induce anti-GnRH antibodies, the subsequent effects on serum levels of testosterone and PSA and the patient overall survival. The study included eight patients with histologically-proven advanced prostate cancer with indication for hormonal therapy, who received seven intramuscular immunizations with Heberprovac within 18 weeks. Anti-GnRH antibody titers, testosterone and PSA levels, as well as clinical parameters were recorded and evaluated. The vaccine was well tolerated. Significant reductions in serum levels of testosterone and PSA were seen after four immunizations. Castrate levels of testosterone were observed in all patients at the end of the immunization schedule, which remained at the lowest level for at least 20 months. In a 10-year follow-up three out of six patients who completed the entire trial survived. In contrast only one out eight patients survived in the same period in a matched randomly selected group receiving standard anti-hormonal treatment. Heberprovac vaccination showed a good security profile, as well as immunological, biochemical and, most importantly, clinical benefit. The vaccinated group displayed survival advantage compared with the reference group that received standard treatment. These results warrant further clinical trials with Heberprovac involving a larger cohort.
Keywords
- advanced prostate cancer
- GnRH/LHRH vaccine
- hormone ablation
- hormone sensitive cancer
- overall survival