Strong vaccine responses during chemotherapy are associated with prolonged cancer survival.
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| 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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| Authors | 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 I Lalisang, Nikki M Loof, Sanne Boekestijn, Willem Jan Krebber, Leon Hooftman, Sonja Visscher, Brent A Blumenstein, Richard B Stead, Winald Gerritsen, Sjoerd H van der Burg |
| Journal | Science translational medicine (Sci Transl Med) Vol. 12 Issue 535 (03 18 2020) ISSN: 1946-6242 [Electronic] United States |
| PMID | 32188726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. |
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