Leiden University Scholarly Publications

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Melief, C.J.M.; Welters, M.J.P.; Vergote, I.; Kroep, J.R.; Kenter, G.G.; Ottevanger, P.B.; ... ; Burg, S.H. van der (2020)

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

Article / Letter to editor
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....Show moreTherapeutic 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.Show less
All authors
Melief, C.J.M.; Welters, M.J.P.; Vergote, I.; Kroep, J.R.; Kenter, G.G.; Ottevanger, P.B.; Tjalma, W.A.A.; Denys, H.; Poelgeest, M.I.E. van; Nijman, H.W.; Reyners, A.K.L.; Velu, T.; Goffin, F.; Lalisang, R.I.; Loof, N.M.; Boekestijn, S.; Krebber, W.J.; Hooftman, L.; Visscher, S.; Blumenstein, B.A.; Stead, R.B.; Gerritsen, W.; Burg, S.H. van der
Date
2020-03-18
Journal
Science Translational Medicine
Volume
12
Issue
535
DOI
doi:10.1126/scitranslmed.aaz8235