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. Blumenstein; Richard B. Stead; Winald Gerritsen; Sjoerd H. van der Burg

doi:10.1126/scitranslmed.aaz8235

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 journal › Article › Academic › peer-review

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 language	English
Article number	8235
Number of pages	12
Journal	Science Translational Medicine
Volume	12
Issue number	535
DOIs	https://doi.org/10.1126/scitranslmed.aaz8235
Publication status	Published - 18 Mar 2020

Keywords

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

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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., van Poelgeest, M. I. E., Nijman, H. W., Reyners, A. K. L., Velu, T., Goffin, F., Lalisang, R., Loof, N. M., Boekestijn, S., Krebber, W. J., Hooftman, L., Visscher, S., ... van der Burg, S. H. (2020). Strong vaccine responses during chemotherapy are associated with prolonged cancer survival. Science Translational Medicine, 12(535), Article 8235. https://doi.org/10.1126/scitranslmed.aaz8235

@article{3221dc17f98c427f9b859687f4534519,

title = "Strong vaccine responses during chemotherapy are associated with prolonged cancer survival",

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.",

keywords = "REGULATORY T-CELLS, CERVICAL-CANCER, CLASS-I, CISPLATIN, E6, LEUKOCYTOSIS, CARBOPLATIN, INDUCTION, NIVOLUMAB, RECURRENT",

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

note = "Publisher Copyright: {\textcopyright} 2020 The Authors.",

year = "2020",

month = mar,

day = "18",

doi = "10.1126/scitranslmed.aaz8235",

language = "English",

volume = "12",

journal = "Science Translational Medicine",

issn = "1946-6234",

publisher = "American Association for the Advancement of Science",

number = "535",

}

Melief, CJM, Welters, MJP, Vergote, I, Kroep, JR, Kenter, GG, Ottevanger, PB, Tjalma, WAA, Denys, H, van Poelgeest, MIE, Nijman, HW, Reyners, AKL, Velu, T, Goffin, F, Lalisang, R, Loof, NM, Boekestijn, S, Krebber, WJ, Hooftman, L, Visscher, S, Blumenstein, BA, Stead, RB, Gerritsen, W & van der Burg, SH 2020, 'Strong vaccine responses during chemotherapy are associated with prolonged cancer survival', Science Translational Medicine, vol. 12, no. 535, 8235. https://doi.org/10.1126/scitranslmed.aaz8235

TY - JOUR

T1 - Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

AU - Melief, Cornelis J. M.

AU - Welters, Marij J. P.

AU - Vergote, Ignace

AU - Kroep, Judith R.

AU - Kenter, Gemma G.

AU - Ottevanger, Petronella B.

AU - Tjalma, Wiebren A. A.

AU - Denys, Hannelore

AU - van Poelgeest, Mariette I. E.

AU - Nijman, Hans W.

AU - Reyners, Anna K. L.

AU - Velu, Thierry

AU - Goffin, Frederic

AU - Lalisang, Roy

AU - Loof, Nikki M.

AU - Boekestijn, Sanne

AU - Krebber, Willem Jan

AU - Hooftman, Leon

AU - Visscher, Sonja

AU - Blumenstein, Brent A.

AU - Stead, Richard B.

AU - Gerritsen, Winald

AU - van der Burg, Sjoerd H.

PY - 2020/3/18

Y1 - 2020/3/18

N2 - 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.

AB - 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.

KW - REGULATORY T-CELLS

KW - CERVICAL-CANCER

KW - CLASS-I

KW - CISPLATIN

KW - E6

KW - LEUKOCYTOSIS

KW - CARBOPLATIN

KW - INDUCTION

KW - NIVOLUMAB

KW - RECURRENT

U2 - 10.1126/scitranslmed.aaz8235

DO - 10.1126/scitranslmed.aaz8235

M3 - Article

C2 - 32188726

SN - 1946-6234

VL - 12

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 535

M1 - 8235

ER -

Strong vaccine responses during chemotherapy are associated with prolonged cancer survival

Abstract

Keywords

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