dc.contributor.author | Arce Vargas, F | |
dc.contributor.author | Furness, AJS | |
dc.contributor.author | Litchfield, K | |
dc.contributor.author | Joshi, K | |
dc.contributor.author | Rosenthal, R | |
dc.contributor.author | Ghorani, E | |
dc.contributor.author | Solomon, I | |
dc.contributor.author | Lesko, MH | |
dc.contributor.author | Ruef, N | |
dc.contributor.author | Roddie, C | |
dc.contributor.author | Henry, JY | |
dc.contributor.author | Spain, L | |
dc.contributor.author | Ben Aissa, A | |
dc.contributor.author | Georgiou, A | |
dc.contributor.author | Wong, YNS | |
dc.contributor.author | Smith, M | |
dc.contributor.author | Strauss, D | |
dc.contributor.author | Hayes, A | |
dc.contributor.author | Nicol, D | |
dc.contributor.author | O'Brien, T | |
dc.contributor.author | Mårtensson, L | |
dc.contributor.author | Ljungars, A | |
dc.contributor.author | Teige, I | |
dc.contributor.author | Frendéus, B | |
dc.contributor.author | TRACERx Melanoma, | |
dc.contributor.author | TRACERx Renal, | |
dc.contributor.author | TRACERx Lung consortia, | |
dc.contributor.author | Pule, M | |
dc.contributor.author | Marafioti, T | |
dc.contributor.author | Gore, M | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Turajlic, S | |
dc.contributor.author | Swanton, C | |
dc.contributor.author | Peggs, KS | |
dc.contributor.author | Quezada, SA | |
dc.date.accessioned | 2020-08-25T15:41:30Z | |
dc.date.issued | 2018-04-09 | |
dc.identifier.citation | Cancer cell, 2018, 33 (4), pp. 649 - 663.e4 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4004 | |
dc.identifier.eissn | 1878-3686 | |
dc.identifier.doi | 10.1016/j.ccell.2018.02.010 | |
dc.description.abstract | With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches. | |
dc.format | Print-Electronic | |
dc.format.extent | 649 - 663.e4 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | TRACERx Melanoma | |
dc.subject | TRACERx Renal | |
dc.subject | TRACERx Lung consortia | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Melanoma | |
dc.subject | Receptors, IgG | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Treatment Outcome | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Female | |
dc.subject | T-Lymphocytes, Regulatory | |
dc.subject | CTLA-4 Antigen | |
dc.subject | Antibodies, Monoclonal, Humanized | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.subject | Ipilimumab | |
dc.title | Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-02-15 | |
rioxxterms.versionofrecord | 10.1016/j.ccell.2018.02.010 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer cell | |
pubs.issue | 4 | |
pubs.notes | Not 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/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
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/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Sarcoma and Melanoma Surgery | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 33 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Melanoma and Kidney Cancer | |
icr.researchteam | Sarcoma and Melanoma Surgery | |
dc.contributor.icrauthor | Furness, Andrew | |
dc.contributor.icrauthor | Spain, Lavinia | |
dc.contributor.icrauthor | Smith, Myles | |