Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

Marie Christine Wulff Westergaard; Rikke Andersen; Chloé Chong; Julie Westerlin Kjeldsen; Magnus Pedersen; Christina Friese; Thomas Hasselager; Henrik Lajer; George Coukos; Michal Bassani-Sternberg; Marco Donia; Inge Marie Svane

doi:10.1038/s41416-019-0384-y

Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

Marie Christine Wulff Westergaard, Rikke Andersen, Chloé Chong, Julie Westerlin Kjeldsen, Magnus Pedersen, Christina Friese, Thomas Hasselager, Henrik Lajer, George Coukos, Michal Bassani-Sternberg, Marco Donia, Inge Marie Svane^*

^*Corresponding author for this work

Department of Clinical Medicine

22 Citations (Scopus)

11 Downloads (Pure)

Abstract

Background: Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens. Methods: Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality. Results: Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3 ⁺ cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro. Conclusion: These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution. Trial Registration: clinicaltrials.gov: NCT02482090.

Original language	English
Journal	British Journal of Cancer
Volume	120
Issue number	4
Pages (from-to)	424-434
Number of pages	11
ISSN	0007-0920
DOIs	https://doi.org/10.1038/s41416-019-0384-y
Publication status	Published - 2019

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Tumour-reactive T cell subsets in the microenvironment of ovarian cancerFinal published version, 1.19 MBLicence: CC BY

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title = "Tumour-reactive T cell subsets in the microenvironment of ovarian cancer",

abstract = " Background: Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens. Methods: Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality. Results: Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3 + cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro. Conclusion: These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution. Trial Registration: clinicaltrials.gov: NCT02482090. ",

author = "Westergaard, {Marie Christine Wulff} and Rikke Andersen and Chlo{\'e} Chong and Kjeldsen, {Julie Westerlin} and Magnus Pedersen and Christina Friese and Thomas Hasselager and Henrik Lajer and George Coukos and Michal Bassani-Sternberg and Marco Donia and Svane, {Inge Marie}",

year = "2019",

doi = "10.1038/s41416-019-0384-y",

language = "English",

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TY - JOUR

T1 - Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

AU - Westergaard, Marie Christine Wulff

AU - Andersen, Rikke

AU - Chong, Chloé

AU - Kjeldsen, Julie Westerlin

AU - Pedersen, Magnus

AU - Friese, Christina

AU - Hasselager, Thomas

AU - Lajer, Henrik

AU - Coukos, George

AU - Bassani-Sternberg, Michal

AU - Donia, Marco

AU - Svane, Inge Marie

PY - 2019

Y1 - 2019

N2 - Background: Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens. Methods: Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality. Results: Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3 + cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro. Conclusion: These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution. Trial Registration: clinicaltrials.gov: NCT02482090.

AB - Background: Solid malignancies are frequently infiltrated with T cells. The success of adoptive cell transfer (ACT) with expanded tumour-infiltrating lymphocytes (TILs) in melanoma warrants its testing in other cancer types. In this preclinical study, we investigated whether clinical-grade TILs could be manufactured from ovarian cancer (OC) tumour specimens. Methods: Thirty-four tumour specimens were obtained from 33 individual patients with OC. TILs were analysed for phenotype, antigen specificity and functionality. Results: Minimally expanded TILs (Young TILs) were successfully established from all patients. Young TILs contained a high frequency of CD3 + cells with a variable CD4/CD8 ratio. TILs could be expanded to clinical numbers. Importantly, recognition of autologous tumour cells was demonstrated in TILs in >50% of the patients. We confirmed with mass spectrometry the presentation of multiple tumour antigens, including peptides derived from the cancer-testis antigen GAGE, which could be recognised by antigen-specific TILs. Antigen-specific TILs could be isolated and further expanded in vitro. Conclusion: These findings support the hypothesis that patients with OC can benefit from ACT with TILs and led to the initiation of a pilot clinical trial at our institution. Trial Registration: clinicaltrials.gov: NCT02482090.

U2 - 10.1038/s41416-019-0384-y

DO - 10.1038/s41416-019-0384-y

M3 - Journal article

C2 - 30718808

AN - SCOPUS:85061196235

SN - 0007-0920

VL - 120

SP - 424

EP - 434

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 4

ER -

Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

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