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1 November 2021
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Cancers within the pleural cavity such as malignant pleural mesothelioma (MPM) are aggressive and typically have poor response to therapies. Immune checkpoint inhibitors have been indicated for second-line use in this disease; however, low expression of PD-L1 has contributed to poor response in patients given monotherapy. Chimeric antigen receptor (CAR) T cells developed to target mesothelin and be delivered to the pleural cavity have shown promise in mouse models, but PD-1/PD-L1 signaling promoted functional exhaustion of these CAR T cells; administration of an anti–PD-1 therapy abrogated this effect. Adusumilli and colleagues therefore conducted a first-in-human phase I clinical trial combining pembrolizumab with intrapleural administration of CAR T cells targeting mesothelin. This trial indicated that this combination was not only feasible and safe but had antitumor efficacy, with two patients with MPM experiencing complete metabolic responses, and persistence of functional CAR T cells was observed. For more information, see the article by Adusumilli and colleagues on page 2748.Close Modal - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Research Briefs
MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING
Yong Zhang; Qifan Yang; Xiangyu Zeng; Manxiang Wang; Shuang Dong; Bin Yang; Xinyi Tu; Ting Wei; Wenzhuan Xie; Chao Zhang; Qiang Guo; Jake A. Kloeber; Yueyu Cao; Guijie Guo; Qin Zhou; Fei Zhao; Jinzhou Huang; Li Liu; Kai Zhang; Mingwei Wang; Ping Yin; Kuntian Luo; Min Deng; Wootae Kim; Jing Hou; Yu Shi; Qian Zhu; Lifeng Chen; Sheng Hu; Junqiu Yue; Guoliang Pi; Zhenkun Lou
Efficacy, Safety, and Biomarker Analysis of Combined PD-L1 (Atezolizumab) and VEGF (Bevacizumab) Blockade in Advanced Malignant Peritoneal Mesothelioma
Kanwal Raghav; Suyu Liu; Michael J. Overman; Anneleis F. Willett; Mark Knafl; Szu-Chin Fu; Anais Malpica; Seema Prasad; Richard E. Royal; Christopher P. Scally; Paul F. Mansfield; Ignacio I. Wistuba; Andrew P. Futreal; Dipen M. Maru; Luisa M. Solis Soto; Edwin R. Parra Cuentas; Honglei Chen; Pamela Villalobos; Anuj Verma; Armeen Mahvash; Patrick Hwu; Patricia Cortazar; Edward McKenna; Cindy Yun; Shannon Dervin; Katja Schulze; Walter C. Darbonne; Ajaykumar C. Morani; Scott Kopetz; Keith F. Fournier; Scott E. Woodman; James C. Yao; Gauri R. Varadhachary; Daniel M. Halperin
Research Articles
A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab
Prasad S. Adusumilli; Marjorie G. Zauderer; Isabelle Rivière; Stephen B. Solomon; Valerie W. Rusch; Roisin E. O'Cearbhaill; Amy Zhu; Waseem Cheema; Navin K. Chintala; Elizabeth Halton; John Pineda; Rocio Perez-Johnston; Kay See Tan; Bobby Daly; Jose A. Araujo Filho; Daniel Ngai; Erin McGee; Alain Vincent; Claudia Diamonte; Jennifer L. Sauter; Shanu Modi; Devanjan Sikder; Brigitte Senechal; Xiuyan Wang; William D. Travis; Mithat Gönen; Charles M. Rudin; Renier J. Brentjens; David R. Jones; Michel Sadelain
The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets
Cornelis M. van Tilburg; Elke Pfaff; Kristian W. Pajtler; Karin P.S. Langenberg; Petra Fiesel; Barbara C. Jones; Gnana Prakash Balasubramanian; Sebastian Stark; Pascal D. Johann; Mirjam Blattner-Johnson; Kathrin Schramm; Nicola Dikow; Steffen Hirsch; Christian Sutter; Kerstin Grund; Arend von Stackelberg; Andreas E. Kulozik; Andrej Lissat; Arndt Borkhardt; Roland Meisel; Dirk Reinhardt; Jan-Henning Klusmann; Gudrun Fleischhack; Stephan Tippelt; Dietrich von Schweinitz; Irene Schmid; Christof M. Kramm; André O. von Bueren; Gabriele Calaminus; Peter Vorwerk; Norbert Graf; Frank Westermann; Matthias Fischer; Angelika Eggert; Birgit Burkhardt; Wilhelm Wößmann; Michaela Nathrath; Stefanie Hecker-Nolting; Michael C. Frühwald; Dominik T. Schneider; Ines B. Brecht; Petra Ketteler; Simone Fulda; Ewa Koscielniak; Michael T. Meister; Monika Scheer; Simone Hettmer; Matthias Schwab; Roman Tremmel; Ingrid Øra; Caroline Hutter; Nicolas U. Gerber; Olli Lohi; Bernarda Kazanowska; Antonis Kattamis; Maria Filippidou; Bianca Goemans; C. Michel Zwaan; Till Milde; Natalie Jäger; Stephan Wolf; David Reuss; Felix Sahm; Andreas von Deimling; Uta Dirksen; Angelika Freitag; Ruth Witt; Peter Lichter; Annette Kopp-Schneider; David T.W. Jones; Jan J. Molenaar; David Capper; Stefan M. Pfister; Olaf Witt
Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers
Peter Horak; Christoph Heining; Simon Kreutzfeldt; Barbara Hutter; Andreas Mock; Jennifer Hüllein; Martina Fröhlich; Sebastian Uhrig; Arne Jahn; Andreas Rump; Laura Gieldon; Lino Möhrmann; Dorothea Hanf; Veronica Teleanu; Christoph E. Heilig; Daniel B. Lipka; Michael Allgäuer; Leo Ruhnke; Andreas Laßmann; Volker Endris; Olaf Neumann; Roland Penzel; Katja Beck; Daniela Richter; Ulrike Winter; Stephan Wolf; Katrin Pfütze; Christina Geörg; Bettina Meißburger; Ivo Buchhalter; Marinela Augustin; Walter E. Aulitzky; Peter Hohenberger; Matthias Kroiss; Peter Schirmacher; Richard F. Schlenk; Ulrich Keilholz; Frederick Klauschen; Gunnar Folprecht; Sebastian Bauer; Jens Thomas Siveke; Christian H. Brandts; Thomas Kindler; Melanie Boerries; Anna L. Illert; Nikolas von Bubnoff; Philipp J. Jost; Karsten Spiekermann; Michael Bitzer; Klaus Schulze-Osthoff; Christof von Kalle; Barbara Klink; Benedikt Brors; Albrecht Stenzinger; Evelin Schröck; Daniel Hübschmann; Wilko Weichert; Hanno Glimm; Stefan Fröhling
Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative
Philippe Aftimos; Mafalda Oliveira; Alexandre Irrthum; Debora Fumagalli; Christos Sotiriou; Einav Nili Gal-Yam; Mark E. Robson; Justin Ndozeng; Angelo Di Leo; Eva M. Ciruelos; Evandro de Azambuja; Giuseppe Viale; Elsemieke D. Scheepers; Giuseppe Curigliano; Judith M. Bliss; Jorge S. Reis-Filho; Marco Colleoni; Marija Balic; Fatima Cardoso; Joan Albanell; Caroline Duhem; Sandrine Marreaud; Dario Romagnoli; Beatriz Rojas; Andrea Gombos; Hans Wildiers; Angel Guerrero-Zotano; Peter Hall; Andrea Bonetti; Karolina Fs Larsson; Martina Degiorgis; Silvia Khodaverdi; Richard Greil; Ásgerdur Sverrisdóttir; Marta Paoli; Ethel Seyll; Sibylle Loibl; Barbro Linderholm; Gabriele Zoppoli; Nancy E. Davidson; Oskar Th Johannsson; Philippe L. Bedard; Sherene Loi; Susan Knox; David A. Cameron; Nadia Harbeck; Maite Lasa Montoya; Mariana Brandão; Andrea Vingiani; Carmela Caballero; Florentine S. Hilbers; Lucy R. Yates; Matteo Benelli; David Venet; Martine J. Piccart
Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial
Suzanne Carreira; Nuria Porta; Sara Arce-Gallego; George Seed; Alba Llop-Guevara; Diletta Bianchini; Pasquale Rescigno; Alec Paschalis; Claudia Bertan; Chloe Baker; Jane Goodall; Susana Miranda; Ruth Riisnaes; Ines Figueiredo; Ana Ferreira; Rita Pereira; Mateus Crespo; Bora Gurel; Daniel Nava Rodrigues; Stephen J. Pettitt; Wei Yuan; Violeta Serra; Jan Rekowski; Christopher J. Lord; Emma Hall; Joaquin Mateo; Johann S. de Bono
Resistance to Durvalumab and Durvalumab plus Tremelimumab Is Associated with Functional STK11 Mutations in Patients with Non–Small Cell Lung Cancer and Is Reversed by STAT3 Knockdown
Nabendu Pore; Song Wu; Nathan Standifer; Maria Jure-Kunkel; Melissa de los Reyes; Yashaswi Shrestha; Rebecca Halpin; Raymond Rothstein; Kathy Mulgrew; Stephen Blackmore; Philip Martin; John Meekin, III; Matthew Griffin; Ina Bisha; Theresa A. Proia; Ricardo J. Miragaia; Ronald Herbst; Ashok Gupta; Shaad E. Abdullah; Rajiv Raja; Melanie M. Frigault; J. Carl Barrett; Phillip A. Dennis; Maria Libera Ascierto; Michael D. Oberst
Enhancer Hijacking Drives Oncogenic BCL11B Expression in Lineage-Ambiguous Stem Cell Leukemia
Lindsey E. Montefiori; Sonja Bendig; Zhaohui Gu; Xiaolong Chen; Petri Pölönen; Xiaotu Ma; Alex Murison; Andy Zeng; Laura Garcia-Prat; Kirsten Dickerson; Ilaria Iacobucci; Sherif Abdelhamed; Ryan Hiltenbrand; Paul E. Mead; Cyrus M. Mehr; Beisi Xu; Zhongshan Cheng; Ti-Cheng Chang; Tamara Westover; Jing Ma; Anna Stengel; Shunsuke Kimura; Chunxu Qu; Marcus B. Valentine; Marissa Rashkovan; Selina Luger; Mark R. Litzow; Jacob M. Rowe; Monique L. den Boer; Victoria Wang; Jun Yin; Steven M. Kornblau; Stephen P. Hunger; Mignon L. Loh; Ching-Hon Pui; Wenjian Yang; Kristine R. Crews; Kathryn G. Roberts; Jun J. Yang; Mary V. Relling; William E. Evans; Wendy Stock; Elisabeth M. Paietta; Adolfo A. Ferrando; Jinghui Zhang; Wolfgang Kern; Torsten Haferlach; Gang Wu; John E. Dick; Jeffery M. Klco; Claudia Haferlach; Charles G. Mullighan
Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia
Leonie Smeenk; Sophie Ottema; Roger Mulet-Lazaro; Anja Ebert; Marije Havermans; Andrea Arricibita Varea; Michaela Fellner; Dorien Pastoors; Stanley van Herk; Claudia Erpelinck-Verschueren; Tim Grob; Remco M. Hoogenboezem; François G. Kavelaars; Daniel R. Matson; Emery H. Bresnick; Eric M. Bindels; Alex Kentsis; Johannes Zuber; Ruud Delwel
Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma
Hai-Feng Zhang; Christopher S. Hughes; Wei Li; Jian-Zhong He; Didier Surdez; Amal M. El-Naggar; Hongwei Cheng; Anna Prudova; Alberto Delaidelli; Gian Luca Negri; Xiaojun Li; Maj Sofie Ørum-Madsen; Michael M. Lizardo; Htoo Zarni Oo; Shane Colborne; Taras Shyp; Renata Scopim-Ribeiro; Colin A. Hammond; Anne-Chloe Dhez; Sofya Langman; Jonathan K.M. Lim; Sonia H.Y. Kung; Amy Li; Anne Steino; Mads Daugaard; Seth J. Parker; Ramon I. Klein Geltink; Rimas J. Orentas; Li-Yan Xu; Gregg B. Morin; Olivier Delattre; Dimiter S. Dimitrov; Poul H. Sorensen
Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma
Francesca Puca; Fei Yu; Caterina Bartolacci; Piergiorgio Pettazzoni; Alessandro Carugo; Emmet Huang-Hobbs; Jintan Liu; Ciro Zanca; Federica Carbone; Edoardo Del Poggetto; Joy Gumin; Pushan Dasgupta; Sahil Seth; Sanjana Srinivasan; Frederick F. Lang; Erik P. Sulman; Philip L. Lorenzi; Lin Tan; Mengrou Shan; Zachary P. Tolstyka; Maureen Kachman; Li Zhang; Sisi Gao; Angela K. Deem; Giannicola Genovese; Pier Paolo Scaglioni; Costas A. Lyssiotis; Andrea Viale; Giulio F. Draetta
AXL Inhibition in Macrophages Stimulates Host-versus-Leukemia Immunity and Eradicates Naïve and Treatment-Resistant Leukemia
Irene Tirado-Gonzalez; Arnaud Descot; Devona Soetopo; Aleksandra Nevmerzhitskaya; Alexander Schäffer; Ivan-Maximilano Kur; Ewelina Czlonka; Carolin Wachtel; Ioanna Tsoukala; Luise Müller; Anna-Lena Schäfer; Maresa Weitmann; Petra Dinse; Emily Alberto; Michèle C. Buck; Jonathan JM. Landry; Bianka Baying; Julia Slotta-Huspenina; Jenny Roesler; Patrick N. Harter; Anne-Sophie Kubasch; Jörn Meinel; Eiman Elwakeel; Elisabeth Strack; Christine Tran Quang; Omar Abdel-Wahab; Marc Schmitz; Andreas Weigert; Tobias Schmid; Uwe Platzbecker; Vladimir Benes; Jacques Ghysdael; Halvard Bonig; Katharina S. Götze; Carla V. Rothlin; Sourav Ghosh; Hind Medyouf
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