Intratumoral nanobody-IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice.
Intratumoral nanobody-IL-2 fusions that bind the tumor extracellular matrix suppress solid tumor growth in mice.
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DOI：
10.1093/pnasnexus/pgac244
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发表时间：
2022-11
期刊：
影响因子：
--
通讯作者：
Hynes, Richard O.
中科院分区：
文献类型：
--
作者：
Lutz, Emi A.;Jailkhani, Noor;Momin, Noor;Huang, Ying;Sheen, Allison;Kang, Byong H.;Wittrup, K. Dane;Hynes, Richard O.
Confining cytokine exposure to the tumors would greatly enhance cancer immunotherapy safety and efficacy. Immunocytokines, cytokines fused to tumor-targeting antibodies, have been developed with this intention, but without significant clinical success to date. A critical limitation is uptake by receptor-expressing cells in the blood, that decreases the dose at the tumor and engenders toxicity. Small-format immunocytokines, constructed with antibody fragments, are hypothesized to improve tumor specificity due to rapid systemic clearance. However, effective design criteria for small-format immunocytokines need further examination. Here, we engineer small interleukin-2 (IL-2) immunocytokines fused to nanobodies with nanomolar to picomolar affinities for the tumor-specific EIIIB domain of fibronectin (also known as EDB). Upon intravenous delivery into immunocompetent mice, such immunocytokines led to similar tumor growth delay as size-matched untargeted IL-2. Intratumoral (i.t.) delivery imparted improved survival dependent on affinity to EIIIB. I.t. administration offers a promising avenue to deliver small-format immunocytokines, given effective affinity for the tumor microenvironment.
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影响因子：
45.3
作者：
FYFE, G;FISHER, RI;LOUIE, AC
通讯作者：
LOUIE, AC
影响因子：
14.9
作者：
Dunbar J;Krawczyk K;Leem J;Marks C;Nowak J;Regep C;Georges G;Kelm S;Popovic B;Deane CM
通讯作者：
Deane CM
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
28.1
作者：
通讯作者：
--
影响因子：
158.5
作者：
Gogas, H;Ioannovich, J;Kirkwood, JM
通讯作者：
Kirkwood, JM