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Sci Transl Med. 2020 Mar 18;12(535). pii: eaaz8235. doi: 10.1126/scitranslmed.aaz8235.

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival.

Author information

1
ISA Pharmaceuticals, J.H. Oortweg 19, 2333 CH Leiden, Netherlands. melief@isa-pharma.com shvdburg@lumc.nl.
2
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
3
Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands.
4
Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
5
Department of Gynecologic Oncology, University Hospital, Leuven Cancer Institute, UZ Herestraat 49, 3000 Leuven, Belgium.
6
Center for Gynecologic Oncology Amsterdam, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
7
Department of Medical Oncology, Nijmegen University Medical Center, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, Netherlands.
8
Multidisciplinary Breast Clinic-Unit Gynecological Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.
9
Department of Medical Oncology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium.
10
Department of Gynecology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
11
Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands.
12
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands.
13
Chirec Cancer Institute, Medical Centre Edith Cavell, Rue Edith Cavell 32, 1180 Brussels, Belgium.
14
Department of Medical Oncology, GROW School of Oncology and Developmental Biology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, Netherlands.
15
ISA Pharmaceuticals, J.H. Oortweg 19, 2333 CH Leiden, Netherlands.
16
Trial Architecture Consulting, 4703 Morgan Dr., Chevy Chase, MD 20815, USA.
17
BioPharma Consulting Services, 691 96th Avenue Southeast, Bellevue, WA 98004, USA.
18
Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, Netherlands. melief@isa-pharma.com shvdburg@lumc.nl.

Abstract

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.

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