Non-viral precision T cell receptor replacement for personalized cell therapy.

Humans Antigens, Neoplasm / genetics Biopsy Cell- and Tissue-Based Therapy / adverse effects Cytokine Release Syndrome / complications Disease Progression Encephalitis / complications Gene Editing Gene Knock-In Techniques Gene Knockout Techniques Genes, T-Cell Receptor alpha Genes, T-Cell Receptor beta Mutation Neoplasms / complications Patient Safety Precision Medicine / adverse effects Receptors, Antigen, T-Cell / genetics T-Lymphocytes / immunology Transgenes / genetics HLA Antigens / immunology CRISPR-Cas Systems

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
03 2023
Historique:
received: 16 06 2022
accepted: 04 11 2022
pubmed: 11 11 2022
medline: 25 3 2023
entrez: 10 11 2022
Statut: ppublish

Résumé

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells

Identifiants

DOI: 10.1038/s41586-022-05531-1 PMID: 36356599 PMC: PMC9768791
pubmed: 36356599
doi: 10.1038/s41586-022-05531-1
pii: 10.1038/s41586-022-05531-1
pmc: PMC9768791
doi:

Substances chimiques

Antigens, Neoplasm 0
Receptors, Antigen, T-Cell 0
HLA Antigens 0

Banques de données

ClinicalTrials.gov
['NCT03970382']

Types de publication

Clinical Trial, Phase I Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

687-696

Subventions

Organisme : NIAID NIH HHS
ID : K08 AI139375
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA244118
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197633
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009120
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2022. The Author(s).

Références

Matsushita, H. et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482, 400–404 (2012).
pubmed: 22318521 pmcid: 3874809 doi: 10.1038/nature10755
van Rooij, N. et al. Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J. Clin. Oncol. 31, e439–e442 (2013).
pubmed: 24043743 doi: 10.1200/JCO.2012.47.7521
Schumacher, T. N. & Schreiber, R. D. Neoantigens in cancer immunotherapy. Science 348, 69–74 (2015).
pubmed: 25838375 doi: 10.1126/science.aaa4971
Gros, A. et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat. Med. 22, 433–438 (2016).
pubmed: 26901407 pmcid: 7446107 doi: 10.1038/nm.4051
Tran, E. et al. Cancer immunotherapy based on mutation-specific CD4
pubmed: 24812403 pmcid: 6686185 doi: 10.1126/science.1251102
Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).
pubmed: 28678784 doi: 10.1038/nature23003
Sahin, U. & Tureci, O. Personalized vaccines for cancer immunotherapy. Science 359, 1355–1360 (2018).
pubmed: 29567706 doi: 10.1126/science.aar7112
Hu, Z. et al. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat. Med. 27, 515–525 (2021).
pubmed: 33479501 pmcid: 8273876 doi: 10.1038/s41591-020-01206-4
Lowery, F. J. et al. Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers. Science https://doi.org/10.1126/science.abl5447 (2022).
Ott, P. A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217–221 (2017).
pubmed: 28678778 pmcid: 5577644 doi: 10.1038/nature22991
Robinson, J. et al. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 43, D423–D431 (2015).
pubmed: 25414341 doi: 10.1093/nar/gku1161
Greenbaum, U., Dumbrava, E. I., Biter, A. B., Haymaker, C. L. & Hong, D. S. Engineered T-cell receptor T cells for cancer immunotherapy. Cancer Immunol. Res. 9, 1252–1261 (2021).
pubmed: 34728535 doi: 10.1158/2326-6066.CIR-21-0269
Peng, S. et al. Sensitive detection and analysis of neoantigen-specific T cell populations from tumors and blood. Cell Rep. 28, 2728–2738.e7 (2019).
pubmed: 31484081 pmcid: 6774618 doi: 10.1016/j.celrep.2019.07.106
Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. & Dudley, M. E. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat. Rev. Cancer 8, 299–308 (2008).
pubmed: 18354418 pmcid: 2553205 doi: 10.1038/nrc2355
Roth, T. L. et al. Reprogramming human T cell function and specificity with non-viral genome targeting. Nature 559, 405–409 (2018).
pubmed: 29995861 pmcid: 6239417 doi: 10.1038/s41586-018-0326-5
Oh, S. A. et al. High-efficiency nonviral CRISPR/Cas9-mediated gene editing of human T cells using plasmid donor DNA. J. Exp. Med. 219, e20211530 (2022).
pubmed: 35452075 pmcid: 9040063 doi: 10.1084/jem.20211530
Eyquem, J. et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543, 113–117 (2017).
pubmed: 28225754 pmcid: 5558614 doi: 10.1038/nature21405
Muller, T. R. et al. Targeted T cell receptor gene editing provides predictable T cell product function for immunotherapy. Cell Rep. Med. 2, 100374 (2021).
pubmed: 34467251 pmcid: 8385324 doi: 10.1016/j.xcrm.2021.100374
Ruggiero, E. et al. CRISPR-based gene disruption and integration of high-avidity, WT1-specific T cell receptors improve antitumor T cell function. Sci. Transl Med. 14, eabg8027 (2022).
pubmed: 35138911 doi: 10.1126/scitranslmed.abg8027
Puig-Saus, C. et al. Landscape analysis of neoepitope-specific T cell responses to immunotherapy. Cancer Res. https://doi.org/10.1158/1538-7445.AM2020-NG11 (2020).
Johnson, L. A. et al. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114, 535–546 (2009).
pubmed: 19451549 pmcid: 2929689 doi: 10.1182/blood-2009-03-211714
Robbins, P. F. et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J. Clin. Oncol. 29, 917–924 (2011).
pubmed: 21282551 pmcid: 3068063 doi: 10.1200/JCO.2010.32.2537
Tran, E. et al. T-cell transfer therapy targeting mutant KRAS in cancer. N. Engl. J. Med. 375, 2255–2262 (2016).
pubmed: 27959684 pmcid: 5178827 doi: 10.1056/NEJMoa1609279
Malekzadeh, P. et al. Neoantigen screening identifies broad TP53 mutant immunogenicity in patients with epithelial cancers. J. Clin. Invest. 129, 1109–1114 (2019).
pubmed: 30714987 doi: 10.1172/JCI123791
Jin, B. Y. et al. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight 3, e99488 (2018).
pubmed: 29669936 pmcid: 5931134 doi: 10.1172/jci.insight.99488
Sanderson, J. P. et al. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology 9, 1682381 (2020).
pubmed: 32002290 doi: 10.1080/2162402X.2019.1682381
Draper, L. M. et al. Targeting of HPV-16
pubmed: 26429982 pmcid: 4603283 doi: 10.1158/1078-0432.CCR-14-3341
Poirot, L. et al. Multiplex genome-edited T-cell manufacturing platform for “off-the-shelf” adoptive T-cell immunotherapies. Cancer Res. 75, 3853–3864 (2015).
pubmed: 26183927 doi: 10.1158/0008-5472.CAN-14-3321
Stadtmauer, E. A. et al. CRISPR-engineered T cells in patients with refractory cancer. Science 367, eaba7365 (2020).
pubmed: 32029687 doi: 10.1126/science.aba7365
Mujib, S. et al. Antigen-independent induction of Tim-3 expression on human T cells by the common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 is associated with proliferation and is dependent on the phosphoinositide 3-kinase pathway. J. Immunol. 188, 3745–3756 (2012).
pubmed: 22422881 doi: 10.4049/jimmunol.1102609
Shevchenko, I. et al. Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses. Oncoimmunology 9, 1744946 (2020).
pubmed: 33457090 pmcid: 7790505 doi: 10.1080/2162402X.2020.1744946
Teachey, D. T. et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 6, 664–679 (2016).
pubmed: 27076371 pmcid: 5448406 doi: 10.1158/2159-8290.CD-16-0040
Wang, M. et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med. 382, 1331–1342 (2020).
pubmed: 32242358 pmcid: 7731441 doi: 10.1056/NEJMoa1914347
Venkatesan, S. et al. Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and cancer evolution. Ann. Oncol. 29, 563–572 (2018).
pubmed: 29324969 pmcid: 5888943 doi: 10.1093/annonc/mdy003
Zhang, J. et al. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature 609, 369–374 (2022).
pubmed: 36045296 pmcid: 9452296 doi: 10.1038/s41586-022-05140-y
Swanton, C., McGranahan, N., Starrett, G. J. & Harris, R. S. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 5, 704–712 (2015).
pubmed: 26091828 pmcid: 4497973 doi: 10.1158/2159-8290.CD-15-0344
McGranahan, N. et al. Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171, 1259–1271.e11 (2017).
pubmed: 29107330 pmcid: 5720478 doi: 10.1016/j.cell.2017.10.001
Doran, S. L. et al. T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, phase I/II study. J. Clin. Oncol. 37, 2759–2768 (2019).
pubmed: 31408414 pmcid: 6800280 doi: 10.1200/JCO.18.02424
Nagarsheth, N. B. et al. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat. Med. 27, 419–425 (2021).
pubmed: 33558725 pmcid: 9620481 doi: 10.1038/s41591-020-01225-1
Kalbasi, A. & Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 20, 25–39 (2020).
pubmed: 31570880 doi: 10.1038/s41577-019-0218-4
Schober, K. et al. Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection. Nat. Immunol. 21, 434–441 (2020).
pubmed: 32205883 doi: 10.1038/s41590-020-0628-2
Wermke, M. et al. Safety and anti-tumor activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses—clinical update on the ACTengine® IMA203 trial. J. Immunother. Cancer https://doi.org/10.1136/jitc-2021-SITC2021.959 (2021).
Hong, D. S. et al.Updated safety and efficacy from SURPASS, the phase I trial of ADP-A2M4CD8, a next-generation autologous T-cell receptor T-cell therapy, in previously treated patients with unresectable or metastatic tumors. Ann. Oncol. 33, S331–S355 (2022).
doi: 10.1016/j.annonc.2022.07.861
Provasi, E. et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 18, 807–815 (2012).
pubmed: 22466705 pmcid: 5019824 doi: 10.1038/nm.2700
Fraietta, J. A. et al. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 558, 307–312 (2018).
pubmed: 29849141 pmcid: 6320248 doi: 10.1038/s41586-018-0178-z
Sen, D. R. et al. The epigenetic landscape of T cell exhaustion. Science 354, 1165–1169 (2016).
pubmed: 27789799 pmcid: 5497589 doi: 10.1126/science.aae0491
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. & Flavell, R. A. Transforming growth factor-β regulation of immune responses. Annu. Rev. Immunol. 24, 99–146 (2006).
pubmed: 16551245 doi: 10.1146/annurev.immunol.24.021605.090737
Schmidt, R. et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science 375, eabj4008 (2022).
pubmed: 35113687 pmcid: 9307090 doi: 10.1126/science.abj4008
Kalbasi, A. et al. Potentiating adoptive cell therapy using synthetic IL-9 receptors. Nature 607, 360–365 (2022).
pubmed: 35676488 pmcid: 9283313 doi: 10.1038/s41586-022-04801-2
Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. Preprint at https://doi.org/10.48550/arXiv.1303.3997 (2013).
Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).
pubmed: 22300766 pmcid: 3290792 doi: 10.1101/gr.129684.111
Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013).
pubmed: 23396013 pmcid: 3833702 doi: 10.1038/nbt.2514
Saunders, C. T. et al. Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs. Bioinformatics 28, 1811–1817 (2012).
pubmed: 22581179 doi: 10.1093/bioinformatics/bts271
Lai, Z. et al. VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res. 44, e108 (2016).
pubmed: 27060149 pmcid: 4914105 doi: 10.1093/nar/gkw227
Dobin, A. & Gingeras, T. R. Mapping RNA-seq reads with STAR. Curr. Protoc Bioinformatics 51, 11.14.1–11.14.19 (2015).
pubmed: 26334920 doi: 10.1002/0471250953.bi1114s51
Szolek, A. et al. OptiType: precision HLA typing from next-generation sequencing data. Bioinformatics 30, 3310–3316 (2014).
pubmed: 25143287 pmcid: 4441069 doi: 10.1093/bioinformatics/btu548
Reynisson, B., Alvarez, B., Paul, S., Peters, B. & Nielsen, M. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 48, W449–W454 (2020).
pubmed: 32406916 pmcid: 7319546 doi: 10.1093/nar/gkaa379
Favero, F. et al. Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data. Ann. Oncol. 26, 64–70 (2015).
pubmed: 25319062 doi: 10.1093/annonc/mdu479
Roth, A. et al. PyClone: statistical inference of clonal population structure in cancer. Nat. Methods 11, 396–398 (2014).
pubmed: 24633410 pmcid: 4864026 doi: 10.1038/nmeth.2883
Chang, M. T. et al. Accelerating discovery of functional mutant alleles in cancer. Cancer Discov. 8, 174–183 (2018).
pubmed: 29247016 doi: 10.1158/2159-8290.CD-17-0321
Power, R. P. et al. A diagnostic platform for precision cancer therapy enabling composite biomarkers by combining tumor and immune features from an enhanced exome and transcriptome. Cancer Res. 80, 1334 (2020).
doi: 10.1158/1538-7445.AM2020-1334
Bolotin, D. A. et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat. Methods 12, 380–381 (2015).
pubmed: 25924071 doi: 10.1038/nmeth.3364
Diaz-Gay, M. et al. Mutational Signatures in Cancer (MuSiCa): a web application to implement mutational signatures analysis in cancer samples. BMC Bioinformatics 19, 224 (2018).
pubmed: 29898651 pmcid: 6001047 doi: 10.1186/s12859-018-2234-y
Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94–101 (2020).
pubmed: 32025018 pmcid: 7054213 doi: 10.1038/s41586-020-1943-3
Smith, C., Ma, Y., Campbell, K. M., Pan, Z. & Stawiski, E. Uncovering HLA loss of heterozygosity in cancer for the improvement of personalized neoTCR immunotherapy with PACT-ESCAPE. Cancer Res. https://doi.org/10.1158/1538-7445.AM2022-1213 (2022).
Robinson, J. et al. IPD-IMGT/HLA database. Nucleic Acids Res. 48, D948–D955 (2020).
pubmed: 31667505
Bratman, S. V. et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat. Cancer 1, 873–881 (2020).
pubmed: 35121950 doi: 10.1038/s43018-020-0096-5
Lybarger, L. et al. Enhanced immune presentation of a single-chain major histocompatibility complex class I molecule engineered to optimize linkage of a C-terminally extended peptide. J. Biol. Chem. 278, 27105–27111 (2003).
pubmed: 12732632 doi: 10.1074/jbc.M303716200
Lefranc, M. P. et al. IMGT®, the international ImMunoGeneTics information system® 25 years on. Nucleic Acids Res. 43, D413–D422 (2015).
pubmed: 25378316 doi: 10.1093/nar/gku1056
Bethune, M. T., Comin-Anduix, B., Hwang Fu, Y. H., Ribas, A. & Baltimore, D. Preparation of peptide–MHC and T-cell receptor dextramers by biotinylated dextran doping. BioTechniques 62, 123–130 (2017).
pubmed: 28298179 doi: 10.2144/000114525

Auteurs

Susan P Foy (SP)

PACT Pharma, South San Francisco, CA, USA. sfoy@pactpharma.com.

Kyle Jacoby (K)

PACT Pharma, South San Francisco, CA, USA.

Daniela A Bota (DA)

Department of Neurology and Chao Family Comprehensive Cancer Center, University of California, Irvine, CA, USA.

Theresa Hunter (T)

PACT Pharma, South San Francisco, CA, USA.
ORCID: 0000-0002-6494-1294

Zheng Pan (Z)

PACT Pharma, South San Francisco, CA, USA.

Eric Stawiski (E)

PACT Pharma, South San Francisco, CA, USA.

Yan Ma (Y)

PACT Pharma, South San Francisco, CA, USA.

William Lu (W)

PACT Pharma, South San Francisco, CA, USA.

Songming Peng (S)

PACT Pharma, South San Francisco, CA, USA.

Clifford L Wang (CL)

PACT Pharma, South San Francisco, CA, USA.

Benjamin Yuen (B)

PACT Pharma, South San Francisco, CA, USA.

Olivier Dalmas (O)

PACT Pharma, South San Francisco, CA, USA.

Katharine Heeringa (K)

PACT Pharma, South San Francisco, CA, USA.

Barbara Sennino (B)

PACT Pharma, South San Francisco, CA, USA.

Andy Conroy (A)

PACT Pharma, South San Francisco, CA, USA.

Michael T Bethune (MT)

PACT Pharma, South San Francisco, CA, USA.

Ines Mende (I)

PACT Pharma, South San Francisco, CA, USA.

William White (W)

PACT Pharma, South San Francisco, CA, USA.

Monica Kukreja (M)

PACT Pharma, South San Francisco, CA, USA.

Swetha Gunturu (S)

PACT Pharma, South San Francisco, CA, USA.

Emily Humphrey (E)

PACT Pharma, South San Francisco, CA, USA.

Adeel Hussaini (A)

PACT Pharma, South San Francisco, CA, USA.

Duo An (D)

PACT Pharma, South San Francisco, CA, USA.

Adam J Litterman (AJ)

PACT Pharma, South San Francisco, CA, USA.

Boi Bryant Quach (BB)

PACT Pharma, South San Francisco, CA, USA.

Alphonsus H C Ng (AHC)

Institute for Systems Biology, Seattle, WA, USA.

Yue Lu (Y)

Institute for Systems Biology, Seattle, WA, USA.

Chad Smith (C)

PACT Pharma, South San Francisco, CA, USA.

Katie M Campbell (KM)

Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
ORCID: 0000-0001-6491-4432

Daniel Anaya (D)

PACT Pharma, South San Francisco, CA, USA.

Lindsey Skrdlant (L)

PACT Pharma, South San Francisco, CA, USA.

Eva Yi-Hsuan Huang (EY)

PACT Pharma, South San Francisco, CA, USA.

Ventura Mendoza (V)

PACT Pharma, South San Francisco, CA, USA.

Jyoti Mathur (J)

PACT Pharma, South San Francisco, CA, USA.

Luke Dengler (L)

PACT Pharma, South San Francisco, CA, USA.

Bhamini Purandare (B)

PACT Pharma, South San Francisco, CA, USA.

Robert Moot (R)

PACT Pharma, South San Francisco, CA, USA.

Michael C Yi (MC)

PACT Pharma, South San Francisco, CA, USA.

Roel Funke (R)

PACT Pharma, South San Francisco, CA, USA.

Alison Sibley (A)

PACT Pharma, South San Francisco, CA, USA.

Todd Stallings-Schmitt (T)

PACT Pharma, South San Francisco, CA, USA.

David Y Oh (DY)

Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, USA.

Bartosz Chmielowski (B)

Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA.
ORCID: 0000-0002-2374-3320

Mehrdad Abedi (M)

Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
ORCID: 0000-0003-4640-0977

Yuan Yuan (Y)

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.

Jeffrey A Sosman (JA)

Department of Medicine and Robert H. Lurie Cancer Center, Northwestern University, Evanston, IL, USA.

Sylvia M Lee (SM)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
ORCID: 0000-0002-7425-2230

Adam J Schoenfeld (AJ)

Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.

David Baltimore (D)

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
ORCID: 0000-0001-8723-8190

James R Heath (JR)

Institute for Systems Biology, Seattle, WA, USA.
ORCID: 0000-0001-5356-4385

Alex Franzusoff (A)

PACT Pharma, South San Francisco, CA, USA.

Antoni Ribas (A)

Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA. ARibas@mednet.ucla.edu.
Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA. ARibas@mednet.ucla.edu.
ORCID: 0000-0003-3669-8458

Arati V Rao (AV)

PACT Pharma, South San Francisco, CA, USA.

Stefanie J Mandl (SJ)

PACT Pharma, South San Francisco, CA, USA. smandl@pactpharma.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Non-viral precision T cell receptor...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes néoplasiques › Non-viral precision T cell receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques cytologiques › Cytodiagnostic › Biopsie › Non-viral precision T cell receptor...
questionsmedicales.fr › Thérapeutique › Biothérapie › Thérapie cellulaire et tissulaire › Non-viral precision T cell receptor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Choc › Syndrome de réponse inflammatoire généralisée › Syndrome de libération de cytokines › Non-viral precision T cell receptor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Non-viral precision T cell receptor...
questionsmedicales.fr › Maladies du système nerveux › Encéphalite › Non-viral precision T cell receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Édition de gène › Non-viral precision T cell receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-in de gènes › Non-viral precision T cell receptor...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-out de gènes › Non-viral precision T cell receptor...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes du récepteur des cellules T › Gènes de la chaine alpha du récepteur des lymphocytes T › Non-viral precision T cell receptor...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes du récepteur des cellules T › Gènes de la chaine bêta du récepteur des lymphocytes T › Non-viral precision T cell receptor...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Non-viral precision T cell receptor...
questionsmedicales.fr › Tumeurs › Non-viral precision T cell receptor...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Accidents › Prévention des accidents › Sécurité › Sécurité des patients › Non-viral precision T cell receptor...
questionsmedicales.fr › Professions de santé › Médecine › Médecine clinique › Médecine de précision › Non-viral precision T cell receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Non-viral precision T cell receptor...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Non-viral precision T cell receptor...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Transgènes › Non-viral precision T cell receptor...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Non-viral precision T cell receptor...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › Non-viral precision T cell receptor...