Show simple item record

dc.contributor.authorKohli, K
dc.contributor.authorYao, L
dc.contributor.authorNowicki, TS
dc.contributor.authorZhang, S
dc.contributor.authorBlack, RG
dc.contributor.authorSchroeder, BA
dc.contributor.authorFarrar, EA
dc.contributor.authorCao, J
dc.contributor.authorSloan, H
dc.contributor.authorStief, D
dc.contributor.authorCranmer, LD
dc.contributor.authorWagner, MJ
dc.contributor.authorHawkins, DS
dc.contributor.authorPillarisetty, VG
dc.contributor.authorRibas, A
dc.contributor.authorCampbell, J
dc.contributor.authorPierce, RH
dc.contributor.authorKim, EY
dc.contributor.authorJones, RL
dc.contributor.authorRiddell, SR
dc.contributor.authorYee, C
dc.contributor.authorPollack, SM
dc.date.accessioned2021-07-29T10:35:45Z
dc.date.available2021-07-29T10:35:45Z
dc.identifier.citationJournal for immunotherapy of cancer, 2021, 9 (5)
dc.identifier.issn2051-1426
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4713
dc.identifier.eissn2051-1426
dc.identifier.eissn2051-1426en_US
dc.identifier.doi10.1136/jitc-2020-002232
dc.identifier.doi10.1136/jitc-2020-002232en_US
dc.description.abstractBackground Synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are ideal solid tumors for the development of adoptive cellular therapy (ACT) targeting NY-ESO-1, as a high frequency of tumors homogeneously express this cancer-testes antigen. Data from early phase clinical trials have shown antitumor activity after the adoptive transfer of NY-ESO-1-specific T cells. In these studies, persistence of NY-ESO-1 specific T cells is highly correlated with response to ACT, but patients often continue to have detectable transferred cells in their peripheral blood following progression.Method We performed a phase I clinical trial evaluating the safety of NY-ESO-1-specific endogenous T cells (ETC) following cyclophosphamide conditioning. Peripheral blood mononuclear cells (PBMCs) from treated patients were evaluated by flow cytometry and gene expression analysis as well as through ex vivo culture assays with and without IL-15.Results Four patients were treated in a cohort using ETC targeting NY-ESO-1 following cyclophosphamide conditioning. Treatment was well tolerated without significant toxicity, but all patients ultimately had disease progression. In two of four patients, we obtained post-treatment tumor tissue and in both, NY-ESO-1 antigen was retained despite clear detectable persisting NY-ESO-1-specific T cells in the peripheral blood. Despite a memory phenotype, these persisting cells lacked markers of proliferation or activation. However, in ex vivo culture assays, they could be induced to proliferate and kill tumor using IL-15. These results were also seen in PBMCs from two patients who received gene-engineered T-cell receptor-based products at other centers.Conclusions ETC targeting NY-ESO-1 with single-agent cyclophosphamide alone conditioning was well tolerated in patients with SS and those with MRCL. IL-15 can induce proliferation and activity in persisting NY-ESO-1-specific T cells even in patients with disease progression following ACT. These results support future work evaluating whether IL-15 could be incorporated into ACT trials post-infusion or at the time of progression.
dc.formatPrint
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.titleIL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy.
dc.typeJournal Article
dcterms.dateAccepted2021-03-19
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1136/jitc-2020-002232
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.relation.isPartOfJournal for immunotherapy of cancer
pubs.issue5
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials (R Jones)/Sarcoma Clinical Trials (R Jones) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume9en_US
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trials (R Jones)
icr.researchteamSarcoma Clinical Trials (R Jones)en_US
dc.contributor.icrauthorJones, Robinen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc/4.0