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Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy

Galstyan, Anna ; Markman, Janet L. ; Shatalova, Ekaterina S. ; Chiechi, Antonella ; Korman, Alan J. ; Patil, Rameshwar ; Klymyshyn, Dmytro ; Tourtellotte, Warren G. ; Israel, Liron L. ; Braubach, Oliver ; Ljubimov, Vladimir A. ; Mashouf, Leila A. ; Ramesh, Arshia ; Grodzinski, Zachary B. ; Penichet, Manuel L. ; Black, Keith L. ; Holler, Eggehard ; Sun, Tao ; Ding, Hui ; Ljubimov, Alexander V. ; Ljubimova, Julia Y.



Abstract

Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood-brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(ss-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 ...

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