Research ArticleCancer

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

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Science Translational Medicine  18 Mar 2020:
Vol. 12, Issue 535, eaaz8235
DOI: 10.1126/scitranslmed.aaz8235

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Vaccinating a cancer away

Despite advances in prevention and early detection, cervical cancer remains prevalent worldwide and continues to cause mortality, thus requiring improved therapeutic interventions. One approach being developed for the treatment of cervical cancer is therapeutic vaccination targeting human papillomavirus 16 (HPV16), a key virus associated with the pathogenesis of this cancer. Melief et al. tested this therapeutic vaccine approach in 77 patients with advanced, recurrent, or metastatic cervical cancer who were also receiving standard chemotherapy with carboplatin and paclitaxel. Almost half of the tumors regressed with the combination therapy. The authors characterized the patients’ immune responses and correlated them with the likelihood of successful treatment.


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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