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.

UR - https://www.nature.com/articles/s41416-019-0425-6#author-information

U2 - 10.1038/s41416-019-0384-y

DO - 10.1038/s41416-019-0384-y

M3 - Journal article

C2 - 30718808

AN - SCOPUS:85061196235

VL - 120

SP - 424

EP - 434

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

SN - 0007-0920

ER -