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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TL;DR: It is shown that even peptide-targeted mutations in the TCR can introduce new reactivities against peptides that bear similarity to the original target, and a novel structure-guided approach for enhancing TCR specificity independent of affinity is explored.
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Niloufar Ataie,Jingyi Xiang,Neal Cheng,Elliott J. Brea,Wenjie Lu,David A. Scheinberg,Cheng Liu,Ho Leung Ng +7 more
TL;DR: A crystal structure is shown in a crystal structure that ESK1 Fab binds to RMF/HLA-A*02:01 in a mode different from that of TCRs, which demonstrates how protein structure information can contribute to personalized immunotherapy.
Journal ArticleDOI
CBFB-MYH11 fusion neoantigen enables T cell recognition and killing of acute myeloid leukemia.
Melinda A. Biernacki,Kimberly A. Foster,Kyle B. Woodward,Michael E. Coon,Carrie Cummings,Tanya Cunningham,Robson G. Dossa,Michelle Brault,Jamie Stokke,Tayla M Olsen,Kelda M. Gardner,Elihu H. Estey,Soheil Meshinchi,Anthony Rongvaux,Anthony Rongvaux,Marie Bleakley +15 more
TL;DR: The data indicate that the CBFB-MYH11 fusion neoantigen is naturally presented on AML blasts and enables T cell recognition and killing of AML and demonstrate that targeting neoantigens has clinical relevance even in low-mutational frequency cancers like fusion-driven AML.
Journal ArticleDOI
Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA
Christopher J. Holland,Rory M. Crean,Johanne M. Pentier,Ben de Wet,Angharad Lloyd,Velupillai Srikannathasan,Nikolai Lissin,Katy A. Lloyd,Thomas Blicher,Paul J. Conroy,Miriam Hock,Robert J. Pengelly,Thomas E. Spinner,Brian Cameron,Elizabeth A. Potter,Anitha Jeyanthan,Peter Eamon Molloy,Malkit Sami,Milos Aleksic,Nathaniel Liddy,Ross A. Robinson,Stephen Harper,Marco Lepore,Christopher R. Pudney,Marc W. van der Kamp,Pierre J. Rizkallah,Bent K. Jakobsen,Annelise Vuidepot,David K. Cole +28 more
TL;DR: It is demonstrated that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains, and TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity.
Journal ArticleDOI
BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors.
Patrizia Comoli,Sabrina Basso,Giovanni Riva,Patrizia Barozzi,Ilaria Guido,Antonella Gurrado,Giuseppe Quartuccio,Laura Rubert,Ivana Lagreca,Daniela Vallerini,Fabio Forghieri,Monica Morselli,Paola Bresciani,Angela Cuoghi,Ambra Paolini,Elisabetta Colaci,Roberto Marasca,Antonio Cuneo,Lorenzo Iughetti,Tommaso Trenti,Franco Narni,Robin Foà,Marco Zecca,Mario Luppi,Leonardo Potenza +24 more
TL;DR: The results show that p190BCR-ABL-specific CTLs are capable of controlling treatment-refractory Ph+ ALL in vivo, and support the development of adoptive immunotherapeutic approaches with BCR-ABl C TLs in Ph+ All.