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Title
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Strong vaccine responses during chemotherapy are associated with prolonged cancer survival
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Science translational medicine. - -
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Publication
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2020
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ISSN
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1946-6234
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DOI
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10.1126/SCITRANSLMED.AAZ8235
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Volume/pages
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12
:535
(2020)
, 12 p.
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Article Reference
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eaaz8235
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ISI
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000520863600006
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Pubmed ID
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32188726
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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