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1 March 2021
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Cover Image
Photomicrographic image of a tumor invasive margin from a syngeneic tumor model (MC38) stained with multiplex immunofluorescence to identify macrophages (F4/80+; Red) in the tumor microenvironment. Polarization state of these macrophages was determined using inducible nitric oxide synthase (iNOS; Green), a marker for M1 polarization, and arginase I (Arg1; Cyan) a marker for M2 polarization. In the tumor margins, 152-fold increase in M1 macrophages were observed with exoIL-12 treatment. These studies provide evidence that exoIL-12 was significantly more potent than rIL12 and enabled systemic anti-tumor immunity by facilitating prolonged local pharmacology and undetectable systemic exposure. The improved therapeutic index achieved in pre-clinical models support further clinical investigation of this powerful cytokine. Read the full article on p. 523. - PDF Icon PDF LinkTable of Contents
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ISSN 1535-7163
EISSN 1538-8514
Highlights
Review
Small Molecule Therapeutics
Author Choice
A Novel CDK2/9 Inhibitor CYC065 Causes Anaphase Catastrophe and Represses Proliferation, Tumorigenesis, and Metastasis in Aneuploid Cancers
Masanori Kawakami; Lisa Maria Mustachio; Yulong Chen; Zibo Chen; Xiuxia Liu; Cheng-Hsin Wei; Jason Roszik; Adam S. Kittai; Alexey V. Danilov; Xiaoshan Zhang; Bingliang Fang; Jing Wang; John V. Heymach; Liliya Tyutyunyk-Massey; Sarah J. Freemantle; Jonathan M. Kurie; Xi Liu; Ethan Dmitrovsky
The Glutaminase Inhibitor CB-839 (Telaglenastat) Enhances the Antimelanoma Activity of T-Cell–Mediated Immunotherapies
Sruthy Varghese; Snigdha Pramanik; Leila J. Williams; Hannah R. Hodges; Courtney W. Hudgens; Grant M. Fischer; Catherine K. Luo; Barbara Knighton; Lin Tan; Philip L. Lorenzi; Andrew L. Mackinnon; Jennifer L. McQuade; Yared Hailemichael; Jason Roszik; Weiyi Peng; Y.N. Vashisht Gopal
Large Molecule Therapeutics
Author Choice
Exosome Surface Display of IL12 Results in Tumor-Retained Pharmacology with Superior Potency and Limited Systemic Exposure Compared with Recombinant IL12
Nuruddeen D. Lewis; Chang Ling Sia; Katherine Kirwin; Sonya Haupt; Gauri Mahimkar; Tong Zi; Ke Xu; Kevin Dooley; Su Chul Jang; Bryan Choi; Adam Boutin; Andrew Grube; Christine McCoy; Jorge Sanchez-Salazar; Michael Doherty; Leonid Gaidukov; Scott Estes; Kyriakos D. Economides; Douglas E. Williams; Sriram Sathyanarayanan
Author Choice
ABBV-085, Antibody–Drug Conjugate Targeting LRRC15, Is Effective in Osteosarcoma: A Report by the Pediatric Preclinical Testing Consortium
Pooja Hingorani; Michael E. Roth; Yifei Wang; Wendong Zhang; Jonathan B. Gill; Douglas J. Harrison; Beverly Teicher; Stephen Erickson; Gregory Gatto; Malcolm A. Smith; Edward A. Kolb; Richard Gorlick
Author Choice
Resistance to Pyrrolobenzodiazepine Dimers Is Associated with SLFN11 Downregulation and Can Be Reversed through Inhibition of ATR
Shenlan Mao; Raghothama Chaerkady; Wen Yu; Gina D’Angelo; Andrew Garcia; Hong Chen; Allison M. Barrett; Sandrina Phipps; Ryan Fleming; Sonja Hess; Jens-Oliver Koopmann; Nazzareno Dimasi; Susan Wilson; Kathryn Pugh; Kimberly Cook; Luke A. Masterson; Changshou Gao; Herren Wu; Ronald Herbst; Philip W. Howard; David A. Tice; Mark Cobbold; Jay Harper
Improved Antitumor Activity of the Fluoropyrimidine Polymer CF10 in Preclinical Colorectal Cancer Models through Distinct Mechanistic and Pharmacologic Properties
William H. Gmeiner; Anthony Dominijanni; Alex O. Haber; Lais P. Ghiraldeli; David L. Caudell; Ralph D’Agostino, Jr; Boris C. Pasche; Thomas L. Smith; Zhiyong Deng; Sezgin Kiren; Chinnadurai Mani; Komaraiah Palle; Jonathan R. Brody
Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers
Cancer Biology and Translational Studies
Author Choice
Targeting Radiation-Resistant Prostate Cancer Stem Cells by B7-H3 CAR T Cells
Yida Zhang; Lile He; Ananthan Sadagopan; Tao Ma; Gianpietro Dotti; Yufeng Wang; Hui Zheng; Xin Gao; Dian Wang; Albert B. DeLeo; Song Fan; Ruochuan Sun; Ling Yu; Liyuan Zhang; Gongxian Wang; Soldano Ferrone; Xinhui Wang
Macrophages Mediate the Antitumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors
Amy Kwan; Natalie Winder; Emer Atkinson; Haider Al-Janabi; Richard J. Allen; Russell Hughes; Mohammed Moamin; Rikah Louie; Dhanajay Evans; Matthew Hutchinson; Drew Capper; Katie Cox; Joshua Handley; Adam Wilshaw; Taewoo Kim; Simon J. Tazzyman; Sanjay Srivastava; Penelope Ottewell; Jayakumar Vadakekolathu; Graham Pockley; Claire E. Lewis; Janet E. Brown; Sarah J. Danson; Joe Conner; Munitta Muthana
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