Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

Cornelis J. M. Melief*, Marij J. P. Welters, Ignace Vergote, Judith R. Kroep, Gemma G. Kenter, Petronella B. Ottevanger, Wiebren A. A. Tjalma, Hannelore Denys, Mariette I. E. van Poelgeest, Hans W. Nijman, Anna K. L. Reyners, Thierry Velu, Frederic Goffin, Roy Lalisang, Nikki M. Loof, Sanne Boekestijn, Willem Jan Krebber, Leon Hooftman, Sonja Visscher, Brent A. BlumensteinRichard B. Stead, Winald Gerritsen, Sjoerd H. van der Burg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

45 Citations (Web of Science)

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.

Original languageEnglish
Article number8235
Number of pages12
JournalScience Translational Medicine
Volume12
Issue number535
DOIs
Publication statusPublished - 18 Mar 2020

Keywords

  • REGULATORY T-CELLS
  • CERVICAL-CANCER
  • CLASS-I
  • CISPLATIN
  • E6
  • LEUKOCYTOSIS
  • CARBOPLATIN
  • INDUCTION
  • NIVOLUMAB
  • RECURRENT

Cite this