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
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
Citations
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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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Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers
Parisa Malekzadeh,Anna Pasetto,Paul F. Robbins,Maria R. Parkhurst,Biman C. Paria,Li Jia,Jared J. Gartner,Victoria Hill,Zhiya Yu,Nicholas P. Restifo,Abraham Sachs,Eric Tran,Winifred Lo,Robert Somerville,Steven A. Rosenberg,Drew C. Deniger +15 more
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TL;DR: Enhancement and exploitation of T-cell cross-priming by cDC1s offer opportunities for improved cancer immunotherapy, including in vivo targeting of tumor antigens to internalizing receptors on c DC1s and strategies to increase their numbers, activation and priming capacity within tumors and tumor-draining lymph nodes.
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Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation.
Marianne Klemp Gjertsen,Jens Bjørheim,Ingvil Saeterdal,June Helen Myklebust,Gustav Gaudernack +4 more
TL;DR: Data demonstrate that peptide vaccination with a single mutant p21‐ras‐derived peptide induces CD4+ and CD8+ CTL specific for nested epitopes, including the Gly → Val substitution at codon 12, and that both these T‐cell sub‐sets specifically recognize tumour cells harbouring the corresponding K‐ras mutation.
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Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial.
Michael Heinrich,Robin L. Jones,Margaret von Mehren,Patrick Schöffski,César Serrano,Yoon-Koo Kang,Philippe A. Cassier,Olivier Mir,Ferry A.L.M. Eskens,William D. Tap,Piotr Rutkowski,Sant P. Chawla,Jonathan C. Trent,Meera Tugnait,Erica Evans,Tamieka Lauz,Teresa Zhou,Maria Roche,Beni B. Wolf,Sebastian Bauer,Suzanne George +20 more
TL;DR: This two-part, open-label, dose-escalation and dose-expansion study aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFra D842V, in patients with advanced gastrointestinal stromal tumours.