Babar Bashir1,2, Melissa A Wilson3. 1. Departments of Medical Oncology, Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 700, Philadelphia, PA, 19107, USA. 2. Department of Pharmacology & Experimental Therapeutics, Thomas Jefferson University, 1020 Locust Street, JAH 368, Philadelphia, PA, 19107, USA. 3. Departments of Medical Oncology, Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 700, Philadelphia, PA, 19107, USA. Melissa.Wilson@jefferson.edu.
Abstract
PURPOSE OF REVIEW: The last decade witnessed an explosion in immunotherapeutic agent approvals for various malignancies. The success of immune checkpoint inhibitors (CTLA-4 and PD-1/PD-L1) in melanoma quickly sprung to other cancer types and are considered the emerging face of oncology. RECENT FINDINGS: Antibodies to CTLA-4 were first to enter the field, quickly followed by PD-1/PD-L1 inhibitors. Combination anti-CTLA4 and anti-PD-1/PD-L1 therapies were investigated, and after demonstrating improved responses, rapidly gained approval. Certain tumor types previously considered non-immunogenic also demonstrated durable responses which has been a remarkable discovery. However, not all tumor types respond to immunotherapies and it is widely recognized that tumor-specific immune inflammatory status predicts the best responders. Ongoing translational work indicates specific upregulation in additional immune checkpoints that circumvent response to anti-CTLA4 and anti-PD-1/PD-L1 antibodies. Here, we provide a comprehensive review of promising therapies on the horizon with unique combinations designed to overcome resistance or expand the pool of treatment responders.
PURPOSE OF REVIEW: The last decade witnessed an explosion in immunotherapeutic agent approvals for various malignancies. The success of immune checkpoint inhibitors (CTLA-4 and PD-1/PD-L1) in melanoma quickly sprung to other cancer types and are considered the emerging face of oncology. RECENT FINDINGS: Antibodies to CTLA-4 were first to enter the field, quickly followed by PD-1/PD-L1 inhibitors. Combination anti-CTLA4 and anti-PD-1/PD-L1 therapies were investigated, and after demonstrating improved responses, rapidly gained approval. Certain tumor types previously considered non-immunogenic also demonstrated durable responses which has been a remarkable discovery. However, not all tumor types respond to immunotherapies and it is widely recognized that tumor-specific immune inflammatory status predicts the best responders. Ongoing translational work indicates specific upregulation in additional immune checkpoints that circumvent response to anti-CTLA4 and anti-PD-1/PD-L1 antibodies. Here, we provide a comprehensive review of promising therapies on the horizon with unique combinations designed to overcome resistance or expand the pool of treatment responders.
Authors: Paolo A Ascierto; Georgina V Long; Caroline Robert; Benjamin Brady; Caroline Dutriaux; Anna Maria Di Giacomo; Laurent Mortier; Jessica C Hassel; Piotr Rutkowski; Catriona McNeil; Ewa Kalinka-Warzocha; Kerry J Savage; Micaela M Hernberg; Celeste Lebbé; Julie Charles; Catalin Mihalcioiu; Vanna Chiarion-Sileni; Cornelia Mauch; Francesco Cognetti; Lars Ny; Ana Arance; Inge Marie Svane; Dirk Schadendorf; Helen Gogas; Abdel Saci; Joel Jiang; Jasmine Rizzo; Victoria Atkinson Journal: JAMA Oncol Date: 2019-02-01 Impact factor: 31.777
Authors: Akira Orimo; Piyush B Gupta; Dennis C Sgroi; Fernando Arenzana-Seisdedos; Thierry Delaunay; Rizwan Naeem; Vincent J Carey; Andrea L Richardson; Robert A Weinberg Journal: Cell Date: 2005-05-06 Impact factor: 41.582
Authors: E M Hersh; M Del Vecchio; M P Brown; R Kefford; C Loquai; A Testori; S Bhatia; R Gutzmer; R Conry; A Haydon; C Robert; S Ernst; J Homsi; J J Grob; K Kendra; S S Agarwala; M Li; A Clawson; C Brachmann; M Karnoub; I Elias; M F Renschler; A Hauschild Journal: Ann Oncol Date: 2015-09-26 Impact factor: 32.976
Authors: Sanjeev Mariathasan; Shannon J Turley; Dorothee Nickles; Alessandra Castiglioni; Kobe Yuen; Yulei Wang; Edward E Kadel; Hartmut Koeppen; Jillian L Astarita; Rafael Cubas; Suchit Jhunjhunwala; Romain Banchereau; Yagai Yang; Yinghui Guan; Cecile Chalouni; James Ziai; Yasin Şenbabaoğlu; Stephen Santoro; Daniel Sheinson; Jeffrey Hung; Jennifer M Giltnane; Andrew A Pierce; Kathryn Mesh; Steve Lianoglou; Johannes Riegler; Richard A D Carano; Pontus Eriksson; Mattias Höglund; Loan Somarriba; Daniel L Halligan; Michiel S van der Heijden; Yohann Loriot; Jonathan E Rosenberg; Lawrence Fong; Ira Mellman; Daniel S Chen; Marjorie Green; Christina Derleth; Gregg D Fine; Priti S Hegde; Richard Bourgon; Thomas Powles Journal: Nature Date: 2018-02-14 Impact factor: 49.962
Authors: Christoph Roderburg; Sven H Loosen; Jan Bednarsch; Patrick H Alizai; Anjali A Roeth; Sophia M Schmitz; Mihael Vucur; Mark Luedde; Pia Paffenholz; Frank Tacke; Christian Trautwein; Tom F Ulmer; Ulf Peter Neumann; Tom Luedde Journal: Int J Mol Sci Date: 2021-06-18 Impact factor: 5.923