Changing the location of proteins on the cell surface is a promising strategy for modulating T cell functions.
T cells
bispecific antibodies
cancer immunotherapy
immune checkpoints
immune synapse
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
01 Jul 2024
01 Jul 2024
Historique:
received:
07
02
2023
accepted:
13
06
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
2
7
2024
Statut:
aheadofprint
Résumé
Targeting immune receptors on T cells is a common strategy to treat cancer and autoimmunity. Frequently, this is accomplished through monoclonal antibodies targeting the ligand binding sites of stimulatory or inhibitory co-receptors. Blocking ligand binding prevents downstream signalling and modulates specific T cell functions. Since 1985, the FDA has approved over 100 monoclonal antibodies against immune receptors. This therapeutic approach significantly improved the care of patients with numerous immune-related conditions; however, many patients are unresponsive, and some develop immune-related adverse events. One reason for that is the lack of consideration for the localization of these receptors on the cell surface of the immune cells in the context of the immune synapse. In addition to blocking ligand binding, changing the location of these receptors on the cell surface within the different compartments of the immunological synapse could serve as an alternative, efficient, and safer approach to treating these patients. This review discusses the potential therapeutic advantages of altering proteins' localization within the immune synapse and summarizes published work in this field. It also discusses the novel use of bispecific antibodies to induce the clustering of receptors on the cell surface. It presents the rationale for developing novel antibodies, targeting the organization of signalling receptor complexes on the cell surface. This approach offers an innovative and emerging technology to treat cancer patients resistant to current immunotherapies.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institutes of Health (USA)
ID : AI125640
Organisme : National Institutes of Health (USA)
ID : CA231277
Organisme : National Institutes of Health (USA)
ID : AI150597
Organisme : National Institutes of Health (USA)
ID : AI175498
Informations de copyright
© 2024 John Wiley & Sons Ltd.
Références
Azoulay‐Alfaguter I, Strazza M, Peled M, Novak HK, Muller J, Dustin ML, et al. The tyrosine phosphatase SHP‐1 promotes T‐cell adhesion by activating the adaptor protein CrkII in the immunological synapse. Sci Signal. 2017;10(491):eaal2880. https://doi.org/10.1126/scisignal.aal2880
Bromley SK, Burack WR, Johnson KG, Somersalo K, Sims TN, Sumen C, et al. The immunological synapse. Annu Rev Immunol. 2001;19:375–396. https://doi.org/10.1146/annurev.immunol.19.1.375
Biolato AM, Filali L, Wurzer H, Hoffmann C, Gargiulo E, Valitutti S, et al. Actin remodeling and vesicular trafficking at the tumor cell side of the immunological synapse direct evasion from cytotoxic lymphocytes. Int Rev Cell Mol Biol. 2020;356:99–130. https://doi.org/10.1016/bs.ircmb.2020.07.001
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 4th ed. New York: Garland Science; 2002 Integrins. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26867/
Alakoskela JM, Koner AL, Rudnicka D, Köhler K, Howarth M, Davis DM. Mechanisms for size‐dependent protein segregation at immune synapses assessed with molecular rulers. Biophys J. 2011;100(12):2865–2874. https://doi.org/10.1016/j.bpj.2011.05.013
Strazza M, Moore EK, Adam K, Azoulay‐Alfaguter I, Mor A. Neutralization of the adaptor protein PAG by monoclonal antibody limits murine tumor growth. Mol Ther Methods Clin Dev. 2022;9(27):380–390. https://doi.org/10.1016/j.omtm.2022.10.012
Cartwright AN, Griggs J, Davis DM. The immune synapse clears and excludes molecules above a size threshold. Nat Commun. 2014;19(5):5479. https://doi.org/10.1038/ncomms6479
Finetti F, Baldari CT. The immunological synapse as a pharmacological target. Pharmacol Res. 2018;134:118–133. https://doi.org/10.1016/j.phrs.2018.06.009
Moore EK, Strazza M, Mor A. Combination approaches to target PD‐1 signaling in cancer. Front Immunol. 2022;14(13):927265. https://doi.org/10.3389/fimmu.2022.927265
Mor A, Strazza M. Bridging the gap: connecting the mechanisms of immune‐related adverse events and autoimmunity through PD‐1. Front Cell Dev Biol. 2022;3(9):790386. https://doi.org/10.3389/fcell.2021.790386
Suzuki K, Tajima M, Tokumaru Y, Oshiro Y, Nagata S, Kamada H, et al. Anti‐PD‐1 antibodies recognizing the membrane‐proximal region are PD‐1 agonists that can down‐regulate inflammatory diseases. Sci Immunol. 2023;8(79):eadd4947. https://doi.org/10.1126/sciimmunol.add4947
Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three‐dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998;395(6697):82–86. https://doi.org/10.1038/25764
Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285(5425):221–227. https://doi.org/10.1126/science.285.5425.221
Dustin ML. What counts in the immunological synapse? Mol Cell. 2014;54(2):255–262. https://doi.org/10.1016/j.molcel.2014.04.001
Al‐Aghbar MA, Jainarayanan AK, Dustin ML, Roffler SR. The interplay between membrane topology and mechanical forces in regulatingregulates T cell receptor activity. Commun Biol. 2022;5(1):40. https://doi.org/10.1038/s42003-021-02995-1
Dustin ML. The immunological synapse. Cancer Immunol Res. 2014;2(11):1023–1033. https://doi.org/10.1158/2326-6066.CIR-14-0161
Yokosuka T, Kobayashi W, Sakata‐Sogawa K, Takamatsu M, Hashimoto‐Tane A, Dustin ML, et al. Spatiotemporal regulation of T cell costimulation by TCR‐CD28 microclusters and protein kinase C theta translocation. Immunity. 2008;29(4):589–601. https://doi.org/10.1016/j.immuni.2008.08.011
Kong KF, Yokosuka T, Canonigo‐Balancio AJ, Isakov N, Saito T, Altman A. A motif in the V3 domain of the kinase PKC‐θ determines its localization in the immunological synapse and functions in T cells via association with CD28. Nat Immunol. 2011;12(11):1105–1112. https://doi.org/10.1038/ni.2120
Riley JL. PD‐1 signaling in primary T cells. Immunol Rev. 2009;229(1):114–125. https://doi.org/10.1111/j.1600-065X.2009.00767.x
Strazza M, Azoulay‐Alfaguter I, Peled M, Adam K, Mor A. Transmembrane adaptor protein PAG is a mediator of PD‐1 inhibitory signaling in human T cells. Commun Biol. 2021;4(1):672. https://doi.org/10.1038/s42003-021-02225-8
Dragovich MA, Adam K, Strazza M, Tocheva AS, Peled M, Mor A. SLAMF6 clustering is required to augment T cell activation. PLoS One. 2019;14(6):e0218109. https://doi.org/10.1371/journal.pone.0218109
Wang Y, Guo H, Feng Z, Wang S, Wang Y, He Q, et al. PD‐1‐targeted discovery of peptide inhibitors by virtual screening, molecular dynamics simulation, and surface plasmon resonance. Molecules. 2019;24(20):3784. https://doi.org/10.3390/molecules24203784
Lötscher J, Líndez MIAA, Kirchhammer N, Cribioli E, Giordano AGMP, Trefny MP, et al. Magnesium sensing via LFA‐1 regulates CD8+T cell effector function. Cell. 2022;185(4):585–602.e29. https://doi.org/10.1016/j.cell.2021.12.039
Wurzer H, Hoffmann C, Al Absi A, Thomas C. Actin cytoskeleton straddling the immunological synapse between cytotoxic lymphocytes and cancer cells. Cells. 2019;8(5):463. https://doi.org/10.3390/cells8050463
Peled M, Tocheva AS, Sandigursky S, Nayak S, Philips EA, Nichols KE, et al. Affinity purification mass spectrometry analysis of PD‐1 uncovers SAP as a new checkpoint inhibitor. Proc Natl Acad Sci U S A. 2018;115(3):E468–E477. https://doi.org/10.1073/pnas.1710437115
Li K, Yuan Z, Lyu J, Ahn E, Davis SJ, Ahmed R, et al. PD‐1 suppresses TCR‐CD8 cooperativity during T‐cell antigen recognition. Nat Commun. 2021;2(1):2746. https://doi.org/10.1038/s41467-021-22965-9
Hao LY, Lerrer S, Song R, Goeckeritz M, Hu X, Mor A. Exclusion of PD‐1 from the immune synapse: a novel strategy to modulate T cell function. bioRxiv [Preprint]. 2023;11(16):566907. https://doi.org/10.1101/2023.11.16.566907
Pentcheva‐Hoang T, Chen L, Pardoll DM, Allison JP. Programmed death‐1 concentration at the immunological synapse is determined by ligand affinity and availability. Proc Natl Acad Sci U S A. 2007;104(45):17765–17770. https://doi.org/10.1073/pnas.0708767104
Yokosuka T, Takamatsu M, Kobayashi‐Imanishi W, Hashimoto‐Tane A, Azuma M, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209(6):1201–1217. https://doi.org/10.1084/jem.20112741
Sheppard KA, Fitz LJ, Lee JM, Benander C, George JA, Wooters J, et al. PD‐1 inhibits T‐cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett. 2004;574(1–3):37–41. https://doi.org/10.1016/j.febslet.2004.07.083
Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD‐1 immunoreceptor inhibits B cell receptor‐mediated signaling by recruiting src homology 2‐domain‐containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci U S A. 2001;98(24):13866–13871. https://doi.org/10.1073/pnas.231486598
Azoulay‐Alfaguter I, Strazza M, Pedoeem A, Mor A. The coreceptor programmed death 1 inhibits T‐cell adhesion by regulating Rap1. J Allergy Clin Immunol. 2015;135(2):564–567. https://doi.org/10.1016/j.jaci.2014.07.055
Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP‐1 and SHP‐2 associate with immunoreceptor tyrosine‐based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 2004;173(2):945–954. https://doi.org/10.4049/jimmunol.173.2.945
Patsoukis N, Brown J, Petkova V, Liu F, Li L, Boussiotis VA. Selective effects of PD‐1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation. Sci Signal. 2012;5(230):1–14. https://doi.org/10.1126/scisignal.2002796
Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, et al. T cell costimulatory receptor CD28 is a primary target for PD‐1‐mediated inhibition. Science. 2017;355(6332):1428–1433. https://doi.org/10.1126/science.aaf1292
Philips EA, Garcia‐España A, Tocheva AS, Ahearn IM, Adam KR, Pan R, et al. The structural features that distinguish PD‐L2 from PD‐L1 emerged in placental mammals. J Biol Chem. 2020;295(14):4372–4380. https://doi.org/10.1074/jbc.AC119.011747
Ellestad KK, Lin J, Boon L, Anderson CC. PD‐1 controls tonic signaling and lymphopenia‐induced proliferation of T lymphocytes. Front Immunol. 2017;12(8):1289. https://doi.org/10.3389/fimmu.2017.01289
Fernandes RA, Su L, Nishiga Y, Ren J, Bhuiyan AM, Cheng N, et al. Immune receptor inhibition through enforced phosphatase recruitment. Nature. 2020;586(7831):779–784. https://doi.org/10.1038/s41586-020-2851-2
Tocheva AS, Peled M, Strazza M, Adam KR, Lerrer S, Nayak S, et al. Quantitative phosphoproteomic analysis reveals involvement of PD‐1 in multiple T cell functions. J Biol Chem. 2020;295(52):18036–18050. https://doi.org/10.1074/jbc.RA120.014745
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet. 2000;25(1):25–29. https://doi.org/10.1038/75556
Dobenecker MW, Schmedt C, Okada M, Tarakhovsky A. The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T‐cell development and function. Mol Cell Biol. 2005;25(23):10533–10542. https://doi.org/10.1128/MCB.25.23.10533-10542.2005
Draberova L, Bugajev V, Potuckova L, Halova I, Bambouskova M, Polakovicova I, et al. Transmembrane adaptor protein PAG/CBP is involved in both positive and negative regulation of mast cell signaling. Mol Cell Biol. 2014;34(23):4285–4300. https://doi.org/10.1128/MCB.00983-14
Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, et al. Whole‐genome landscapes of major melanoma subtypes. Nature. 2017;545(7653):175–180. https://doi.org/10.1038/nature22071
Tedoldi S, Paterson JC, Hansmann ML, Natkunam Y, Rüdiger T, Angelisova P, et al. Transmembrane adaptor molecules: a new category of lymphoid‐cell markers. Blood. 2006;107(1):213–221. https://doi.org/10.1182/blood-2005-06-2273
Carrasco‐Padilla C, Hernaiz‐Esteban A, Álvarez‐Vallina L, Aguilar‐Sopeña O, Roda‐Navarro P. Bispecific antibody format and the Organization of Immunological Synapses in T cell‐redirecting strategies for cancer immunotherapy. Pharmaceutics. 2022;15(1):132. https://doi.org/10.3390/pharmaceutics15010132
Urbanska K, Lynn RC, Stashwick C, Thakur A, Lum LG, Powell DJ Jr. Targeted cancer immunotherapy via combination of designer bispecific antibody and novel gene‐engineered T cells. J Transl Med. 2014;13(12):347. https://doi.org/10.1186/s12967-014-0347-2
Segués A, Huang S, Sijts A, Berraondo P, Zaiss DM. Opportunities and challenges of bi‐specific antibodies. Int Rev Cell Mol Biol. 2022;369:45–70. https://doi.org/10.1016/bs.ircmb.2022.05.001
Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019;18(8):585–608. https://doi.org/10.1038/s41573-019-0028-1
Gaumann AK, Kiefer F, Alfer J, Lang SA, Geissler EK, Breier G. Receptor tyrosine kinase inhibitors: are they real tumor killers? Int J Cancer. 2016;138(3):540–554. https://doi.org/10.1002/ijc.29499
Anselmo AC, Gokarn Y, Mitragotri S. Non‐invasive delivery strategies for biologics. Nat Rev Drug Discov. 2019;18(1):19–40. https://doi.org/10.1038/nrd.2018.183
Girard N. New strategies and novel combinations in EGFR TKI‐resistant non‐small cell lung cancer. Curr Treat Options Oncol. 2022;23(11):1626–1644. https://doi.org/10.1007/s11864-022-01022-7
Schram AM, Odintsov I, Espinosa‐Cotton M, Khodos I, Sisso WJ, Mattar MS, et al. Zenocutuzumab, a HER2xHER3 bispecific antibody, is effective therapy for tumors driven by NRG1 gene rearrangements. Cancer Discov. 2022;12(5):1233–1247. https://doi.org/10.1158/2159-8290.CD-21-1119
Peng J, Zhu Q, Peng Z, Chen Z, Liu Y, Liu B. Patients with positive HER‐2 amplification advanced gastroesophageal junction cancer achieved complete response with combined chemotherapy of AK104/cadonilimab (PD‐1/CTLA‐4 bispecific): a case report. Front Immunol. 2022;8(13):1049518. https://doi.org/10.3389/fimmu.2022.1049518
Cannons JL, Tangye SG, Schwartzberg PL. SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol. 2011;29:665–705. https://doi.org/10.1146/annurev-immunol-030409-101302
Gartshteyn Y, Askanase AD, Mor A. SLAM associated protein signaling in T cells: tilting the balance toward autoimmunity. Front Immunol. 2021;16(12):654839. https://doi.org/10.3389/fimmu.2021.654839
Gartshteyn Y, Askanase AD, Song R, Bukhari S, Dragovich M, Adam K, et al. SLAMF6 compartmentalization enhances T cell functions. Life Sci Alliance. 2022;6(2):e202201533. https://doi.org/10.26508/lsa.202201533
Dragovich MA, Mor A. The SLAM family receptors: potential therapeutic targets for inflammatory and autoimmune diseases. Autoimmun Rev. 2018;17(7):674–682. https://doi.org/10.1016/j.autrev.2018.01.018
Yigit B, Wang N, Herzog RW, Terhorst C. SLAMF6 in health and disease: Implications for therapeutic targeting. Clin Immunol. 2019;204:3–13. https://doi.org/10.1016/j.clim.2018.10.013
Ren J, Jo Y, Picton LK, Su LL, Raulet DH, Garcia KC. Induced CD45 proximity potentiates natural killer cell receptor antagonism. ACS Synth Biol. 2022;11(10):3426–3439. https://doi.org/10.1021/acssynbio.2c00337
Masarova L, Kantarjian H, Garcia‐Mannero G, Ravandi F, Sharma P, Daver N. Harnessing the immune system against leukemia: monoclonal antibodies and checkpoint strategies for AML. Adv Exp Med Biol. 2017;995:73–95. https://doi.org/10.1007/978-3-319-53156-4_4
Orozco JJ, Kenoyer AL, Lin Y, O'Steen S, Guel R, Nartea ME, et al. Therapy of myeloid leukemia using novel bispecific fusion proteins targeting CD45 and 90Y‐DOTA. Mol Cancer Ther. 2020;19(12):2575–2584. https://doi.org/10.1158/1535-7163.MCT-20-0306
Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, et al. Rescue of exhausted CD8 T cells by PD‐1‐targeted therapies is CD28‐dependent. Science. 2017;355(6332):1423–1427. https://doi.org/10.1126/science.aaf0683
Cotton AD, Nguyen DP, Gramespacher JA, Seiple IB, Wells JA. Development of antibody‐based PROTACs for the degradation of the cell‐surface immune checkpoint protein PD‐L1. J Am Chem Soc. 2021;143(2):593–598. https://doi.org/10.1021/jacs.0c10008
Marei H, Tsai WK, Kee YS, Ruiz K, He J, Cox C, et al. Antibody targeting of E3 ubiquitin ligases for receptor degradation. Nature. 2022;610(7930):182–189. https://doi.org/10.1038/s41586-022-05235-6
Zhou S, Liu M, Ren F, Meng X, Yu J. The landscape of bispecific T cell engager in cancer treatment. Biomark Res. 2021;9(1):38. https://doi.org/10.1186/s40364-021-00294-9
Huo Y, Sheng Z, Lu DR, Ellwanger DC, Li CM, Homann O, et al. Blinatumomab‐induced T cell activation at single cell transcriptome resolution. BMC Genomics. 2021;22(1):145. https://doi.org/10.1186/s12864-021-07435-2
Pinchinat A, Gupta S, Cooper SL, Rau RE. SOHO state of the art updates and next questions | optimal timing of blinatumomab for the treatment of B‐acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2022;23:159–167. https://doi.org/10.1016/j.clml.2022.12.011
Cho BC, Simi A, Sabari J, Vijayaraghavan S, Moores S, Spira A. Amivantamab, an epidermal growth factor receptor (EGFR) and mesenchymal‐epithelial transition factor (MET) bispecific antibody, designed to enable multiple mechanisms of action and broad clinical applications. Clin Lung Cancer. 2022;24:89–97. https://doi.org/10.1016/j.cllc.2022.11.004
Horn LA, Ciavattone NG, Atkinson R, Woldergerima N, Wolf J, Clements VK, et al. CD3xPDL1 bi‐specific T cell engager (BiTE) simultaneously activates T cells and NKT cells, kills PDL1+ tumor cells, and extends the survival of tumor‐bearing humanized mice. Oncotarget. 2017;8(35):57964–57980. https://doi.org/10.18632/oncotarget.19865
Dao T, Pankov D, Scott A, Korontsvit T, Zakhaleva V, Xu Y, et al. Therapeutic bispecific T‐cell engager antibody targeting the intracellular oncoprotein WT1. Nat Biotechnol. 2015;33(10):1079–1086. https://doi.org/10.1038/nbt.3349
Huang Q, Cai WQ, Han ZW, Wang MY, Zhou Y, Cheng JT, et al. Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses. Am J Cancer Res. 2021;11(6):2430–2455.
Kuo TC, Chen A, Harrabi O, Sockolosky JT, Zhang A, Sangalang E, et al. Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti‐tumor activity. J Hematol Oncol. 2020;13(1):160. https://doi.org/10.1186/s13045-020-00989-w
Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, et al. Development and preliminary clinical activity of PD‐1‐guided CTLA‐4 blocking bispecific DART molecule. Cell Rep Med. 2020;1(9):100163. https://doi.org/10.1016/j.xcrm.2020.100163
Wei SC, Anang NAS, Sharma R, Andrews MC, Reuben A, Levine JH, et al. Combination anti‐CTLA‐4 plus anti‐PD‐1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies. Proc Natl Acad Sci U S A. 2019;116(45):22699–22709. https://doi.org/10.1073/pnas.1821218116
Saito T. Molecular dynamics of Co‐signal molecules in T‐cell activation. Adv Exp Med Biol. 2019;1189:135–152. https://doi.org/10.1007/978-981-32-9717-3_5
Alon R, Dustin ML. Force as a facilitator of integrin conformational changes during leukocyte arrest on blood vessels and antigen‐presenting cells. Immunity. 2007;26(1):17–27. https://doi.org/10.1016/j.immuni.2007.01.002
Dadwal N, Mix C, Reinhold A, Witte A, Freund C, Schraven B, et al. The multiple roles of the cytosolic adapter proteins ADAP, SKAP1 and SKAP2 for TCR/CD3‐mediated signaling events. Front Immunol. 2021;6(12):703534. https://doi.org/10.3389/fimmu.2021.703534