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1 May 2022
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Despite the major improvement to cancer outcomes with the development of checkpoint inhibitors, many patients will not respond or will develop resistance to these therapies. As strategies to dually target pathways that are complementary against immunoregulation may relieve these issues, Muik and colleagues generated a bispecific antibody targeting both the PD-1/PD-L1 axis and 4-1BB costimulation (DuoBody-PD-L1×4-1BB, GEN1046), which showed activation of antitumor immunity that was mediated by T-cell response and was superior in mouse models to current clinically approved PD-(L)1 inhibitors. GEN1046 was further tested in a first-in-human phase I/IIa dose-escalation study of 61 patients with advanced, heavily pretreated, refractory solid tumors and demonstrated safety as well as early clinical activity, suggesting that this developed bispecific antibody could be used in patients with checkpoint inhibitor–relapsed or refractory disease. For more information, see the article by Muik and colleagues on page 1248.Close Modal - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements
Alison M. Schram; Igor Odintsov; Madelyn Espinosa-Cotton; Inna Khodos; Whitney J. Sisso; Marissa S. Mattar; Allan J.W. Lui; Morana Vojnic; Sara H. Shameem; Thrusha Chauhan; Jean Torrisi; Jim Ford; Marie N. O'Connor; Cecile A.W. Geuijen; Ron C.J. Schackmann; Jeroen J. Lammerts van Bueren; Ernesto Wasserman; Elisa de Stanchina; Eileen M. O'Reilly; Marc Ladanyi; Alexander Drilon; Romel Somwar
Research Articles
Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors
Alexander Muik; Elena Garralda; Isil Altintas; Friederike Gieseke; Ravit Geva; Eytan Ben-Ami; Corinne Maurice-Dror; Emiliano Calvo; Patricia M. LoRusso; Guzman Alonso; Maria E. Rodriguez-Ruiz; Kristina B. Schoedel; Jordan M. Blum; Bianca Sänger; Theodora W. Salcedo; Saskia M. Burm; Eliana Stanganello; Dennis Verzijl; Fulvia Vascotto; Angelica Sette; Juliane Quinkhardt; Theo S. Plantinga; Aras Toker; Edward N. van den Brink; Mark Fereshteh; Mustafa Diken; David Satijn; Sebastian Kreiter; Esther C.W. Breij; Gaurav Bajaj; Eleni Lagkadinou; Kate Sasser; Özlem Türeci; Ulf Forssmann; Tahamtan Ahmadi; Uğur Şahin; Maria Jure-Kunkel; Ignacio Melero
The European MAPPYACTS Trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies
Pablo Berlanga; Gaelle Pierron; Ludovic Lacroix; Mathieu Chicard; Tiphaine Adam de Beaumais; Antonin Marchais; Anne C. Harttrampf; Yasmine Iddir; Alicia Larive; Aroa Soriano Fernandez; Imene Hezam; Cecile Chevassus; Virginie Bernard; Sophie Cotteret; Jean-Yves Scoazec; Arnaud Gauthier; Samuel Abbou; Nadege Corradini; Nicolas André; Isabelle Aerts; Estelle Thebaud; Michela Casanova; Cormac Owens; Raquel Hladun-Alvaro; Stefan Michiels; Olivier Delattre; Gilles Vassal; Gudrun Schleiermacher; Birgit Geoerger
The Genomics of Colorectal Cancer in Populations with African and European Ancestry
Parvathi A. Myer; Jessica K. Lee; Russell W. Madison; Kith Pradhan; Justin Y. Newberg; Carmen R. Isasi; Samuel J. Klempner; Garrett M. Frampton; Jeffery S. Ross; Jeffrey M. Venstrom; Alexa B. Schrock; Sudipto Das; Leonard Augenlicht; Amit Verma; John M. Greally; Srilakshmi M. Raj; Sanjay Goel; Siraj M. Ali
Genomic and Single-Cell Landscape Reveals Novel Drivers and Therapeutic Vulnerabilities of Transformed Cutaneous T-cell Lymphoma
Xiaofei Song; Shiun Chang; Lucia Seminario-Vidal; Alvaro de Mingo Pulido; Leticia Tordesillas; Xingzhi Song; Rhianna A. Reed; Andrea Harkins; Shannen Whiddon; Jonathan V. Nguyen; Carlos Moran Segura; Chaomei Zhang; Sean Yoder; Zena Sayegh; Yun Zhao; Jane L. Messina; Carly M. Harro; Xiaohui Zhang; José R. Conejo-Garcia; Anders Berglund; Lubomir Sokol; Jianhua Zhang; Paulo C. Rodriguez; James J. Mulé; Andrew P. Futreal; Kenneth Y. Tsai; Pei-Ling Chen
Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis
Kevin Kleffman; Grace Levinson; Indigo V.L. Rose; Lili M. Blumenberg; Sorin A.A. Shadaloey; Avantika Dhabaria; Eitan Wong; Francisco Galán-Echevarría; Alcida Karz; Diana Argibay; Richard Von Itter; Alfredo Floristán; Gillian Baptiste; Nicole M. Eskow; James A. Tranos; Jenny Chen; Eleazar C. Vega y Saenz de Miera; Melissa Call; Robert Rogers; George Jour; Youssef Zaim Wadghiri; Iman Osman; Yue-Ming Li; Paul Mathews; Ronald B. DeMattos; Beatrix Ueberheide; Kelly V. Ruggles; Shane A. Liddelow; Robert J. Schneider; Eva Hernando
Dietary Lactobacillus-Derived Exopolysaccharide Enhances Immune-Checkpoint Blockade Therapy
Hirotaka Kawanabe-Matsuda; Kazuyoshi Takeda; Marie Nakamura; Seiya Makino; Takahiro Karasaki; Kazuhiro Kakimi; Megumi Nishimukai; Tatsukuni Ohno; Jumpei Omi; Kuniyuki Kano; Akiharu Uwamizu; Hideo Yagita; Ivo Gomperts Boneca; Gérard Eberl; Junken Aoki; Mark J. Smyth; Ko Okumura
Tumor ENPP1 (CD203a)/Haptoglobin Axis Exploits Myeloid-Derived Suppressor Cells to Promote Post-Radiotherapy Local Recurrence in Breast Cancer
Borja Ruiz-Fernández de Córdoba; Haritz Moreno; Karmele Valencia; Naiara Perurena; Pablo Ruedas; Thomas Walle; Alberto Pezonaga-Torres; Juan Hinojosa; Elisabet Guruceaga; Antonio Pineda-Lucena; Marta Abengózar-Muela; Denis Cochonneau; Carolina Zandueta; Susana Martínez-Canarias; Álvaro Teijeira; Daniel Ajona; Sergio Ortiz-Espinosa; Xabier Morales; Carlos Ortiz de Solórzano; Marta Santisteban; Luis I. Ramos-García; Laura Guembe; Vratislav Strnad; Dominique Heymann; Sandra Hervás-Stubbs; Rubén Pío; María E. Rodríguez-Ruiz; Carlos E. de Andrea; Silvestre Vicent; Ignacio Melero; Fernando Lecanda; Rafael Martínez-Monge
EGFR Inhibition Potentiates FGFR Inhibitor Therapy and Overcomes Resistance in FGFR2 Fusion–Positive Cholangiocarcinoma
Qibiao Wu; Yuanli Zhen; Lei Shi; Phuong Vu; Patricia Greninger; Ramzi Adil; Joshua Merritt; Regina Egan; Meng-Ju Wu; Xunqin Yin; Cristina R. Ferrone; Vikram Deshpande; Islam Baiev; Christopher J. Pinto; Daniel E. McLoughlin; Charlotte S. Walmsley; James R. Stone; John D. Gordan; Andrew X. Zhu; Dejan Juric; Lipika Goyal; Cyril H. Benes; Nabeel Bardeesy
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