Cancer Vaccines; Papillomavirus E7 Proteins; Papillomavirus Vaccines; Female; Human papillomavirus 16; Humans; Papillomavirus Infections; Uterine Cervical Neoplasms; Medicine (all); General Medicine
Abstract :
[en] Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.
Disciplines :
Immunology & infectious disease
Author, co-author :
Melief, Cornelis J M ; ISA Pharmaceuticals, J.H. Oortweg 19, 2333 CH Leiden, Netherlands. melief@isa-pharma.com shvdburg@lumc.nl ; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Welters, Marij J P ; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands ; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Vergote, Ignace ; Department of Gynecologic Oncology, University Hospital, Leuven Cancer Institute, UZ Herestraat 49, 3000 Leuven, Belgium
Kroep, Judith R ; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Kenter, Gemma G; Center for Gynecologic Oncology Amsterdam, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
Ottevanger, Petronella B; Department of Medical Oncology, Nijmegen University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, Netherlands
Tjalma, Wiebren A A ; Multidisciplinary Breast Clinic-Unit Gynecological Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
Denys, Hannelore; Department of Medical Oncology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium
van Poelgeest, Mariette I E; Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Nijman, Hans W ; Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands
Reyners, Anna K L ; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands
Velu, Thierry ; Chirec Cancer Institute, Medical Centre Edith Cavell, Rue Edith Cavell 32, 1180 Brussels, Belgium
Goffin, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR) ; Chirec Cancer Institute, Medical Centre Edith Cavell, Rue Edith Cavell 32, 1180 Brussels, Belgium
Lalisang, Roy I ; Department of Medical Oncology, GROW School of Oncology and Developmental Biology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, Netherlands
Loof, Nikki M; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands ; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Boekestijn, Sanne; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands ; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
Krebber, Willem Jan; ISA Pharmaceuticals, J.H. Oortweg 19, 2333 CH Leiden, Netherlands
Blumenstein, Brent A ; Trial Architecture Consulting, 4703 Morgan Dr., Chevy Chase, MD 20815, USA
Stead, Richard B ; BioPharma Consulting Services, 691 96th Avenue Southeast, Bellevue, WA 98004, USA
Gerritsen, Winald ; Department of Medical Oncology, Nijmegen University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, Netherlands
van der Burg, Sjoerd H ; Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands. melief@isa-pharma.com shvdburg@lumc.nl ; Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
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