652 Anti-PD-L1/IL-15 KD033 activated macrophages and induced anti-tumor immunity in the tumor-microenvironment
نویسندگان
چکیده
Background KD033 is a clinical-stage bispecific fusion molecule consisting of high-affinity anti-human-PD-L1 antibody and human IL-15. Previous studies with in mice expressing functional PD-1 PD-L1 showed that was efficacious reducing the growth both positive negative tumors. 1 In microenvironment tumors, would still be expressed by some immune cells such as macrophages. The goal current study to evaluate direct effect on macrophages through vitro assess its contribution anti-tumor immunity. Methods Monocyte-derived were treated either KD033, non-targeting IL15 counterpart (ntKD033) or anti-PD-L1 vitro, supernatants analyzed for cytokine/chemokine secretion. Human-PD-1/PD-L1 transgenic C57BL/6 subcutaneously transplanted human-PD-L1 MC38 colon carcinoma intravenously when tumors reached 100 mm 3 . Tumor infiltrating cell populations evaluated Immunohistochemistry (IHC). Results cultures induced secrete inflammatory cytokines IFNγ much higher level compared ntKD033 at same concentrations. alone did not induce IFNγ. IHC KD033-treated PD-1/PD-L1 have similar levels CD8 T tumor infiltrations. macrophage marker CD68 CD68/IFNγ double infiltrations correlated increased inhibitions. Conclusions Increased secretion from IHC. We hypothesized our anti-PD-L1/IL15 induces immunity activating PD-L1-expressing microenvironment. Reference 1. Martomo S, et al. Single-Dose anti–PD-L1/IL-15 protein generates synergistic antitumor robust tumor-immune gene signatures memory responses. Mol Cancer Ther 2021; 20 (2):347–356. Ethics Approval Mouse conducted Kadmon Wuxi AppTec Inc. All procedures related animal handling, care treatment performed according guidelines approved Institutional Animal Care Use Committee (IACUC) WuXi following guidance Association Assessment Accreditation Laboratory (AAALAC).
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ژورنال
عنوان ژورنال: Journal for ImmunoTherapy of Cancer
سال: 2021
ISSN: ['2051-1426']
DOI: https://doi.org/10.1136/jitc-2021-sitc2021.652