Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.
Arce Vargas, F
Ben Aissa, A
TRACERx Lung consortia
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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<sup>+</sup> 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.
TRACERx Lung consortia
Cell Line, Tumor
Xenograft Model Antitumor Assays
Polymorphism, Single Nucleotide
Antibodies, Monoclonal, Humanized
Antineoplastic Agents, Immunological
Melanoma and Kidney Cancer
Sarcoma and Melanoma Surgery
License start date
Cancer cell, 2018, 33 (4), pp. 649 - 663.e4
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0
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