Journal ArticleDOI
Targeting public neoantigens for cancer immunotherapy.
Alexander H. Pearlman,Alexander H. Pearlman,Michael S. Hwang,Maximilian F. Konig,Emily Han-Chung Hsiue,Emily Han-Chung Hsiue,Jacqueline Douglass,Jacqueline Douglass,Sarah R. DiNapoli,Sarah R. DiNapoli,Brian J. Mog,Chetan Bettegowda,Drew M. Pardoll,Sandra B. Gabelli,Nicholas Papadopoulos,Kenneth W. Kinzler,Bert Vogelstein,Shibin Zhou +17 more
- Vol. 2, Iss: 5, pp 487-497
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TLDR
The opportunities and challenges involved in the identification of suitable public neoantigen targets and the development of therapeutic agents targeting them are reviewed.Abstract:
Several current immunotherapy approaches target private neoantigens derived from mutations that are unique to individual patients’ tumors. However, immunotherapeutic agents can also be developed against public neoantigens derived from recurrent mutations in cancer driver genes. The latter approaches target proteins that are indispensable for tumor growth, and each therapeutic agent can be applied to numerous patients. Here we review the opportunities and challenges involved in the identification of suitable public neoantigen targets and the development of therapeutic agents targeting them. Zhou and colleagues discuss the opportunities and challenges in targeting public neoantigens for cancer immunotherapy.read more
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Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs
Mark Yarmarkovich,Quinlen F. Marshall,John M. Warrington,Rasika Premaratne,Alvin Farrel,David Groff,Wei Li,Moreno Di Marco,Erin Runbeck,Hau Truong,Jugmohit S. Toor,Sarvind Tripathi,Son Nguyen,Helena Shen,Tiffany Noel,Nicole L. Church,Amber K. Weiner,Nathan M. Kendsersky,Daniel Martinez,Rebecca Weisberg,Molly Christie,Laurence C. Eisenlohr,Kristopher R. Bosse,Kristopher R. Bosse,Dimiter S. Dimitrov,Stefan Stevanovic,Nikolaos G. Sgourakis,Ben R. Kiefel,John M. Maris,John M. Maris +29 more
TL;DR: In this article, a peptide-centric chimeric antigen receptor (CAR) was proposed to target unmutated peptide QYNPIRTTF, discovered on HLA-A*24:02, derived from the neuroblastoma dependency gene and master transcriptional regulator PHOX2B.
Journal ArticleDOI
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects
TL;DR: The differing mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs are described and both classical and emerging pre-clinical strategies for antigen-specific TCR discovery, enhancement, and validation are discussed.
Journal ArticleDOI
Neoantigens: promising targets for cancer therapy
TL;DR: Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations, such as genomic mutation, dysregulated RNA splicing, disordered post-translational modification, and integrated viral open reading frames as mentioned in this paper .
Journal ArticleDOI
Thermal immuno-nanomedicine in cancer
Zhe Yang,Di Gao,Jing Zhao,Gaojie Yang,Mingli Guo,Yiming Wang,Xuechun Ren,Jong Seung Kim,L. Jin,Zhongmin Tian,Jing Zhang +10 more
Journal ArticleDOI
Translating recent advances in the pathogenesis of acute myeloid leukemia to the clinic
TL;DR: In this review, Bewersdorf and Abdel-Wahab discuss the development of promising new molecular targeted approaches for AML, including menin inhibition, novel IDH1/2 inhibitors, and preclinical means to target TET2, ASXL1, and RNA splicing factor mutations.
References
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Cancer and the Immune System: Basic Concepts and Targets for Intervention
TL;DR: Combination strategies of vaccination together with inhibitors of immunologic checkpoints and agonists for co-stimulatory pathways are proving capable of overcoming tolerance and generating significant anti-tumor responses even in cases of established metastatic cancer.
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The Emerging Landscape of Immune Cell Therapies.
TL;DR: This perspective will summarize the current status of immune cell therapies for cancer, infectious disease, and autoimmunity, and discuss advances in cellular engineering to overcome barriers to progress.
Journal ArticleDOI
Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.
Alex Davenport,Ryan S. Cross,Ryan S. Cross,Kimberly A. Watson,Yang Liao,Wei Shi,Henry Miles Prince,Paul A. Beavis,Joseph A. Trapani,Michael H. Kershaw,David Ritchie,Phillip K. Darcy,Paul J Neeson,Misty R. Jenkins +13 more
TL;DR: A mechanism for how CAR-T cells can debulk large tumor burden quickly is provided and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell.
Journal ArticleDOI
Deep learning using tumor HLA peptide mass spectrometry datasets improves neoantigen identification
Brendan Bulik-Sullivan,Jennifer Busby,Christine D. Palmer,Matthew J. Davis,Tyler Murphy,Andrew Clark,Michele Busby,Fujiko Duke,Aaron Yang,Lauren Young,Noelle C Ojo,Kamilah Caldwell,Jesse Abhyankar,Thomas Boucher,Meghan G. Hart,Vladimir Makarov,Vincent Thomas de Montpréville,Olaf Mercier,Timothy A. Chan,Giorgio V. Scagliotti,Paolo Bironzo,Silvia Novello,Niki Karachaliou,Rafael Rosell,Ian Anderson,Nashat Gabrail,John Hrom,Chainarong Limvarapuss,Karin Choquette,Alexander I. Spira,Raphael Rousseau,Cynthia Voong,Naiyer A. Rizvi,Elie Fadel,Mark G. Frattini,Karin Jooss,Mojca Skoberne,Joshua M. Francis,Roman Yelensky +38 more
TL;DR: This work applies deep learning to a large HLA peptide and genomic dataset from various human tumors to create a computational model of antigen presentation for neoantigen prediction, and shows that this model, named EDGE, increases the positive predictive value of HLA antigen prediction by up to ninefold.
Journal ArticleDOI
Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Zhuting Hu,Donna E. Leet,Rosa Lundbye Allesøe,Giacomo Oliveira,Shuqiang Li,Shuqiang Li,Adrienne M. Luoma,Jinyan Liu,Juliet Forman,Juliet Forman,Teddy Huang,J. Bryan Iorgulescu,J. Bryan Iorgulescu,Rebecca L. Holden,Siranush Sarkizova,Satyen H. Gohil,Satyen H. Gohil,Satyen H. Gohil,Robert A. Redd,Jing Sun,Liudmila Elagina,Anita Giobbie-Hurder,Wandi Zhang,Lauren Peter,Zoe B. Ciantra,Scott J. Rodig,Scott J. Rodig,Oriol Olive,Keerthi Shetty,Jason Pyrdol,Mohamed Uduman,Patrick C. Lee,Pavan Bachireddy,Elizabeth I. Buchbinder,Elizabeth I. Buchbinder,Charles H. Yoon,Charles H. Yoon,Donna Neuberg,Bradley L. Pentelute,Bradley L. Pentelute,Nir Hacohen,Nir Hacohen,Kenneth J. Livak,Sachet A. Shukla,Sachet A. Shukla,Lars Rønn Olsen,Lars Rønn Olsen,Dan H. Barouch,Dan H. Barouch,Dan H. Barouch,Kai W. Wucherpfennig,Edward F. Fritsch,Edward F. Fritsch,Derin B. Keskin,Derin B. Keskin,Catherine J. Wu,Patrick A. Ott +56 more
TL;DR: In this paper, the authors evaluated the long-term effects of personal neoantigen vaccines and found that they can induce durable and specific memory T cell clones that have cytotoxic gene signatures and can diversify to include non-vaccine specificities.