PURPOSE: Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancer. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded autologous dendritic cells (DC) were evaluated as cellular tumor vaccine in a case series of cervical cancer patients. METHODS: Autologous monocyte-derived DCs were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoprotein and administered to 15 stage IV cervical cancer patients. Safety, toxicity, and induction of serological and cellular immune responses were monitored. RESULTS: The vaccine was well-tolerated and no local or systemic side effects or toxicity were recorded. A specific serologic response was seen in 3/11 evaluated patients. Specific cellular immune responses (4/11) were detected with 2/10 positive de novo reactions plus one boosted preexistent response in proliferation assays and 3/11 in IFN-gamma ELISpot assays. A transient drop in tumor marker SCC was observed in 5/9 evaluable patients but did not correlate with markers of the immune response. No objective clinical response was observed. Tumor biopsies available from four patients showed severe or complete loss of HLA expression in three of the advanced tumors. CONCLUSION: Autologous dendritic cells pulsed with HPV E7 protein can induce T cell responses in a portion of late stage cervical cancer patients. Boosting of immune responses by adjuvants and vaccination of tumor HLA-positive patients will be mandatory in future trials.
PURPOSE:Human papillomavirus (HPV) type 16 and 18 are the most prevalent genotypes in cervical cancer. The viral oncoproteins E6 and E7 are considered to be tumor-specific targets for immunotherapy. HPV E7 antigen-loaded autologous dendritic cells (DC) were evaluated as cellular tumor vaccine in a case series of cervical cancerpatients. METHODS: Autologous monocyte-derived DCs were pulsed with recombinant HPV16 E7 or HPV18 E7 oncoprotein and administered to 15 stage IV cervical cancerpatients. Safety, toxicity, and induction of serological and cellular immune responses were monitored. RESULTS: The vaccine was well-tolerated and no local or systemic side effects or toxicity were recorded. A specific serologic response was seen in 3/11 evaluated patients. Specific cellular immune responses (4/11) were detected with 2/10 positive de novo reactions plus one boosted preexistent response in proliferation assays and 3/11 in IFN-gamma ELISpot assays. A transient drop in tumor marker SCC was observed in 5/9 evaluable patients but did not correlate with markers of the immune response. No objective clinical response was observed. Tumor biopsies available from four patients showed severe or complete loss of HLA expression in three of the advanced tumors. CONCLUSION: Autologous dendritic cells pulsed with HPV E7 protein can induce T cell responses in a portion of late stage cervical cancerpatients. Boosting of immune responses by adjuvants and vaccination of tumor HLA-positive patients will be mandatory in future trials.
Authors: M E Ressing; W J van Driel; R M Brandt; G G Kenter; J H de Jong; T Bauknecht; G J Fleuren; P Hoogerhout; R Offringa; A Sette; E Celis; H Grey; B J Trimbos; W M Kast; C J Melief Journal: J Immunother Date: 2000 Mar-Apr Impact factor: 4.456
Authors: A D Santin; P L Hermonat; A Ravaggi; M Chiriva-Internati; D Zhan; S Pecorelli; G P Parham; M J Cannon Journal: J Virol Date: 1999-07 Impact factor: 5.103
Authors: M Adams; L Borysiewicz; A Fiander; S Man; B Jasani; H Navabi; C Lipetz; A S Evans; M Mason Journal: Vaccine Date: 2001-03-21 Impact factor: 3.641
Authors: R Höpfl; K Heim; N Christensen; K Zumbach; U Wieland; B Volgger; A Widschwendter; S Haimbuchner; E Müller-Holzner; M Pawlita; H Pfister; P Fritsch Journal: Lancet Date: 2000-12-09 Impact factor: 79.321
Authors: S Honma; S Tsukada; S Honda; M Nakamura; K Takakuwa; T Maruhashi; S Kodama; K Kanazawa; T Takahashi; K Tanaka Journal: Int J Cancer Date: 1994-06-01 Impact factor: 7.396
Authors: M E Ressing; A Sette; R M Brandt; J Ruppert; P A Wentworth; M Hartman; C Oseroff; H M Grey; C J Melief; W M Kast Journal: J Immunol Date: 1995-06-01 Impact factor: 5.422
Authors: F V Cromme; P F van Bommel; J M Walboomers; M P Gallee; P L Stern; P Kenemans; T J Helmerhorst; M J Stukart; C J Meijer Journal: Br J Cancer Date: 1994-06 Impact factor: 7.640
Authors: Sanja Stevanović; Lindsey M Draper; Michelle M Langhan; Tracy E Campbell; Mei Li Kwong; John R Wunderlich; Mark E Dudley; James C Yang; Richard M Sherry; Udai S Kammula; Nicholas P Restifo; Steven A Rosenberg; Christian S Hinrichs Journal: J Clin Oncol Date: 2015-03-30 Impact factor: 44.544