Granted Patent
B2
US 12,297,249 · App. 18/616,055 · Granted May 13, 2025
Interleukin-2 agents and uses thereof
Inventors:
Scott Moore Carlson (Boston, MA); Gregory Babcock (Marlborough, MA); Zachary Shriver (Winchester, MA); Boopathy Ramakrishnan (Braintree, MA)
Assignee:
Visterra, Inc.
View Patent ↗
Loading inventors, assignments & file history…
Abstract
IL-2 agents that comprise IL-2 variants are disclosed as well as methods, compositions, and uses thereof. The IL-2 agents described herein can be used to treat and/or prevent various disorders and conditions.
Claims (13)
1. An IL-2 conjugate comprising an IL-2 variant and an Fc region, wherein the IL-2 variant comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1 and amino acid substitutions H16L, V69A, and Q74P.
2. The IL-2 conjugate of claim 1 , wherein the IL-2 variant comprises an amino acid sequence set forth in SEQ ID NO: 5.
3. The IL-2 conjugate of claim 1 , wherein the Fc region comprises an Fc region of IgG1.
4. The IL-2 conjugate of claim 3 , wherein the Fc region of IgG1 comprises an amino acid substitution N297G according to EU numbering.
5. The IL-2 conjugate of claim 3 , wherein the Fc region comprises an Fc region of human IgG1 allotype m3.
6. The IL-2 conjugate of claim 3 , wherein the Fc region comprises an amino acid sequence set forth in SEQ ID NO: 1003.
7. The IL-2 conjugate of claim 1 , wherein the IL-2 conjugate is a fusion protein.
8. The IL-2 conjugate of claim 7 , wherein the Fc region is fused to the C-terminus of the IL-2 variant.
9. The IL-2 conjugate of claim 7 , wherein the fusion protein comprises a linker between the IL-2 variant and the Fc region.
10. The IL-2 conjugate of claim 9 , wherein the linker comprises an amino acid sequence set forth in SEQ ID NO: 48.
11. The IL-2 conjugate of claim 7 , wherein the fusion protein forms a dimer.
12. The IL-2 conjugate of claim 11 , wherein the dimer is a homodimer.
13. An IL-2 conjugate comprising an IL-2 variant and an Fc region, wherein the IL-2 conjugate is a fusion protein comprising an amino acid sequence set forth in SEQ ID NO: 1008.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 30, 2024
From: CARLSON, SCOTT MOORE; BABCOCK, GREGORY; SHRIVER, ZACHARY; RAMAKRISHNAN, BOOPATHY
To: VISTERRA, INC.
Reel/Frame 068126/0028 →
Continuity (4)
Provisional Application
62983061
· Feb 28, 2020
Provisional Application
62879137
· Jul 26, 2019
References Cited (238)
US 4908433A
· Mertelsmann et al.
· 1990
[cited by applicant]
US 5466447A
· Abels et al.
· 1995
[cited by applicant]
US 5525491A
· Huston et al.
· 1996
[cited by applicant]
US 7569215B2
· Wittrup et al.
· 2009
[cited by applicant]
US 7951360B2
· Wittrup et al.
· 2011
[cited by applicant]
US 8349311B2
· Wittrup et al.
· 2013
[cited by applicant]
US 9266938B2
· Ast et al.
· 2016
[cited by applicant]
US 9289493B2
· Ko
· 2016
[cited by applicant]
US 9359415B2
· Alvarez et al.
· 2016
[cited by applicant]
US 9428563B2
· Alvarez
· 2016
[cited by applicant]
US 9447159B2
· Ast et al.
· 2016
[cited by applicant]
US 9546203B2
· Kannan
· 2017
[cited by applicant]
US 9580486B2
· Gavin et al.
· 2017
[cited by applicant]
US 9616105B2
· Paulsen et al.
· 2017
[cited by applicant]
US 9669071B2
· Klatzmann et al.
· 2017
[cited by applicant]
US 9732134B2
· Gavin et al.
· 2017
[cited by applicant]
US 9844582B2
· Wittrup et al.
· 2017
[cited by applicant]
US 9932380B2
· Gavin et al.
· 2018
[cited by applicant]
US 20030195154A1
· Walker et al.
· 2003
[cited by applicant]
US 20060160187A1
· Denis-mize et al.
· 2006
[cited by applicant]
US 20060234205A1
· Cao et al.
· 2006
[cited by applicant]
US 20110150826A1
· Paulsen et al.
· 2011
[cited by applicant]
US 20190169254A1
· Higginson-scott et al.
· 2019
[cited by applicant]
US 20190322765A1
· Ast et al.
· 2019
[cited by applicant]
US 20190352363A1
· Seidel et al.
· 2019
[cited by applicant]
US 20190375812A1
· Greve
· 2019
[cited by applicant]
US 20200040053A1
· Alvarez
· 2020
[cited by applicant]
US 20210047382A1
· Greve
· 2021
[cited by applicant]
US 20210070828A1
· Greve
· 2021
[cited by applicant]
US 20210277085A1
· Higginson-scott et al.
· 2021
[cited by applicant]
US 20220226442A1
· Carlson et al.
· 2022
[cited by applicant]
US 20230390360A1
· Schachter et al.
· 2023
[cited by applicant]
CA 2982362A1
· 2016
[cited by applicant]
CN 105143253A
· 2015
[cited by applicant]
CN 109071623A
· 2018
[cited by applicant]
EP 0262802A2
· 1988
[cited by applicant]
EP 0573551B1
· 2003
[cited by applicant]
EP 2673294B1
· 2016
[cited by applicant]
EP 2640411B1
· 2017
[cited by applicant]
EP 3280725A2
· 2018
[cited by applicant]
EP 2859015B1
· 2018
[cited by applicant]
EP 2882458B1
· 2018
[cited by applicant]
EP 2683395B1
· 2018
[cited by applicant]
EP 3075745B1
· 2018
[cited by applicant]
EP 2702074B1
· 2018
[cited by applicant]
EP 3102595B1
· 2018
[cited by applicant]
EP 3180020B1
· 2018
[cited by applicant]
EP 2970441B1
· 2019
[cited by applicant]
EP 2970423B1
· 2019
[cited by applicant]
EP 3489255A1
· 2019
[cited by applicant]
EP 3587444A1
· 2020
[cited by applicant]
EP 3630163A1
· 2020
[cited by applicant]
EP 3443979B1
· 2020
[cited by applicant]
EP 3482766B1
· 2020
[cited by applicant]
EP 2382228B1
· 2020
[cited by applicant]
EP 3766513A1
· 2021
[cited by applicant]
JP 5651583B2
· 2014
[cited by applicant]
JP 5766124B2
· 2015
[cited by applicant]
JP 5878182B2
· 2016
[cited by applicant]
JP 2016514161A
· 2016
[cited by applicant]
JP 2016518823A
· 2016
[cited by applicant]
JP 5972355B2
· 2016
[cited by applicant]
JP 6054889B2
· 2016
[cited by applicant]
JP 6155300B2
· 2017
[cited by applicant]
JP 6306201B2
· 2018
[cited by applicant]
JP 2018512151A
· 2018
[cited by applicant]
JP 6416855B2
· 2018
[cited by applicant]
JP 6450365B2
· 2018
[cited by applicant]
JP 6480409B2
· 2019
[cited by applicant]
JP 6526561B2
· 2019
[cited by applicant]
JP 6559607B2
· 2019
[cited by applicant]
JP 6640834B2
· 2020
[cited by applicant]
JP 2020511949A
· 2020
[cited by applicant]
JP 6768633B2
· 2020
[cited by applicant]
JP 2021006038A
· 2021
[cited by applicant]
SG 11201708349VA
· 2017
[cited by applicant]
WO 8809344A1
· 1988
[cited by applicant]
WO 9215682A1
· 1992
[cited by applicant]
WO 9320849A1
· 1993
[cited by applicant]
WO 9511922A1
· 1995
[cited by applicant]
WO 9960128A1
· 1999
[cited by applicant]
WO 03015697A2
· 2003
[cited by applicant]
WO 2005007121A2
· 2005
[cited by applicant]
WO 2005086751A2
· 2005
[cited by applicant]
WO 2005086798A2
· 2005
[cited by applicant]
WO 2008003473A2
· 2008
[cited by applicant]
WO 2009061853A2
· 2009
[cited by applicant]
WO 2009135615A2
· 2009
[cited by applicant]
WO 2010021519A2
· 2010
[cited by applicant]
WO 2010021520A2
· 2010
[cited by applicant]
WO 2010021521A2
· 2010
[cited by applicant]
WO 2010021522A2
· 2010
[cited by applicant]
WO 2010021523A2
· 2010
[cited by applicant]
WO 2010021524A2
· 2010
[cited by applicant]
WO 2010021525A2
· 2010
[cited by applicant]
WO 2010021526A2
· 2010
[cited by applicant]
WO 2010021527A2
· 2010
[cited by applicant]
WO 2010085495A1
· 2010
[cited by applicant]
WO 2012065212A1
· 2012
[cited by applicant]
WO 2012107417A1
· 2012
[cited by applicant]
WO 2012123381A1
· 2012
[cited by applicant]
WO 2012146628A1
· 2012
[cited by applicant]
WO 2013177187A2
· 2013
[cited by applicant]
WO 2013184938A2
· 2013
[cited by applicant]
WO 2013184939A2
· 2013
[cited by applicant]
WO 2013184942A1
· 2013
[cited by applicant]
WO 2014023752A1
· 2014
[cited by applicant]
WO 2014153111A2
· 2014
[cited by applicant]
WO WO2014153063A1
· 2014
[cited by examiner]
WO 2015118016A1
· 2015
[cited by applicant]
WO 2016014428A2
· 2016
[cited by applicant]
WO 2016025385A1
· 2016
[cited by applicant]
WO 2016164937A2
· 2016
[cited by applicant]
WO 2017014679A2
· 2017
[cited by applicant]
WO 2016164937A9
· 2018
[cited by applicant]
WO 2018089420A1
· 2018
[cited by applicant]
WO 2018119114A1
· 2018
[cited by applicant]
WO 2018217989A1
· 2018
[cited by applicant]
WO 2019010224A1
· 2019
[cited by applicant]
WO 2019070726A1
· 2019
[cited by applicant]
WO 2019112852A1
· 2019
[cited by applicant]
WO 2019112854A1
· 2019
[cited by applicant]
WO 2019125732A1
· 2019
[cited by applicant]
WO 2020020783A1
· 2020
[cited by applicant]
WO 2021021606A1
· 2021
[cited by applicant]
WO 2022120224A1
· 2022
[cited by applicant]
WO 2022159590A1
· 2022
[cited by applicant]
WO 2023102463A1
· 2023
[cited by applicant]
WO 2023154870A1
· 2023
[cited by applicant]
Borrok et al. Journal of Pharmaceutical Sciences 106 (2017) 1008-1017.
[cited by examiner]
International Search Report and Written Opinion for PCT/US2022/013141 dated Jun. 3, 2022 (17 pages).
[cited by applicant]
International Search Report for PCT/US2020/043416 dated Dec. 18, 2020 (8 pages).
[cited by applicant]
International Search Report for PCT/US2021/061883 dated Apr. 7, 2022 (7 pages).
[cited by applicant]
International Search Report for PCT/US2022/080728 dated Mar. 22, 2023 (7 pages).
[cited by applicant]
International Search Report for PCT/US2023/062395 dated May 25, 2023 (5 pages).
[cited by applicant]
“Regulatory Cells and Clinical Application”, Jiang (Ed.), Springer, 2008, excerpt from pp. 17, 19, 20, 29, 43, 58, 70, 77-78, 80, 94, 97, 135-136, and 261.
[cited by applicant]
“Transplant Rejection”, UVA Health, 2023, retrieved from URL: https://uvahealth.com/services/transplant/transplant-rejection.
[cited by applicant]
Adams, Gill , et al., “Targeting cytokines to inflammation sites”, Nature Biotechnology, vol. 21, No. 11, Nov. 2003, pp. 1314-1320, DOI: 10.1038/nbt888 (7 pages).
[cited by applicant]
Adeegbe, Dennis , et al., “Cutting Edge: Allogeneic CD4+CD25+Foxp3+ T Regulatory Cells Suppress Autoimmunity while Establishing Transplantation Tolerance”, The Journal of Immunology, vol. 176, No. 12, 2006, pp. 7149-715…
[cited by applicant]
Ahmadzadeh, Mojgan , et al., “IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients”, Blood, vol. 107, 2006, pp. 2409-2414, DOI: 10.1182/blood-2005-06-2399 (6 pages).
[cited by applicant]
Allan, Sarah E., et al., “Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production”, International Immunology, vol. 19, No. 4, 2007, pp. 345-354, DOI: 10.1093/intimm/dxm0…
[cited by applicant]
Arai, Ryoichi , et al., “Design of the linkers which effectively separate domains of a bifunctional fusion protein”, Protein Engineering, Design and Selection, vol. 14, No. 8, 2001, pp. 529-532, DOI: 10.1093/protein/14.…
[cited by applicant]
Argos, Patrick , “An Investigation of Oligopeptides Linking Domains in Protein Tertiary Structures and Possible Candidates for General Gene Fusion”, Journal of Molecular Biology, vol. 211, 1990, pp. 943-958 (16 pages).
[cited by applicant]
Bachmann, Martin F., et al., “Interleukin 2: from immunostimulation to immunoregulation and back again”, EMBO Reports, vol. 3, No. 12, 2007, pp. 1142-1148 (7 pages).
[cited by applicant]
Bell, Charles J.M., et al., “Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells”, Journal of Autoimmunity, vol. 56, 2015, pp. 66-80 (15 pages).
[cited by applicant]
Bensinger, Steven J., et al., “Distinct IL-2 Receptor Signaling Pattern in CD4+CD25+ Regulatory T Cells”, The Journal of Immunology, vol. 172, 2004, pp. 5287-5296, DOI: 10.4049/jimmunol.172.9.5287 (11 pages).
[cited by applicant]
Boyman, Onur , et al., “Potential use of IL-2/anti-IL-2 antibody immune complexes for the treatment of cancer and autoimmune disease”, Expert Opinion on Biological Therapy, vol. 6, No. 12, 2006, pp. 1323-1331, DOI: 10.1…
[cited by applicant]
Brusko, Todd M., et al., “Human regulatory T cells: role in autoimmune disease and therapeutic opportunities”, Immunological Reviews, vol. 223, 2008, pp. 371-390 (21 pages).
[cited by applicant]
Carmenate, Tania , et al., “Human IL-2 Mutein with Higher Antitumor Efficacy Than Wild Type IL-2”, The Journal of Immunology, vol. 190, No. 12, Jun. 15, 2013, pp. 6230-6238, DOI: 10.4049/jimmunol.1201895, (10 pages).
[cited by applicant]
Cassell, Delanie J., et al., “Therapeutic Enhancement of IL-2 Through Molecular Design”, Current Pharmaceutical Design, vol. 8, 2002, pp. 2171-2183 (13 pages).
[cited by applicant]
Chen, Weiguo , et al., “Signal transducer and activator of transcript signals in allergic disease”, Current reviews of allergy and clinical immunology, J Allergy Clin Immunol, vol. 119, No. 3, Mar. 2007, pp. 529-541, DO…
[cited by applicant]
Eisenstein, Eli M., et al., “The Treg/Th17 Cell Balance: A New Paradigm for Autoimmunity”, Pediatric Research, vol. 65, No. 5, Pt. 2, 2009, pp. 26R-31R (6 pages).
[cited by applicant]
Farhat, Ali M., et al., “Modeling cell-specific dynamics and regulation of the common gamma chain cytokines”, Cell Reports, vol. 35, No. 10944, Apr. 27, 2021, pp. 1-13, e1-e5, DOI: 10.1016/j.celrep.2021.109044 (19 pages…
[cited by applicant]
Fujii, Hodaka , et al., “Activation of Stat5 by interleukin 2 requires a carobxyl-terminal region of the interleukin 2 receptor β chain but is not essential for the proliferative signal transmission”, Proceedings of the…
[cited by applicant]
Goodson, Robert J., et al., “Site-directed pegylation of recombinant interleukin-2 at its glycosylation site”, Bio/Technology, vol. 8, Apr. 1990, pp. 343-345 (4 pages).
[cited by applicant]
Heaton, Keith M., et al., “Characterization of Lymphokine-Activated Killing by Human Peripheral Blood Mononuclear Cells Stimulated with Interleukin 2 (IL-2) Analogs Specific for the Intermediate Affinity IL-2 Receptor”,…
[cited by applicant]
Hernandez, Rosmely , et al., “Engineering IL-2 for immunotherapy of autoimmunity and cancer”, Nature Reviews Immunology, vol. 22, 2022, pp. 614-628, DOI: 10.1038/s41577-022-00680-w (15 pages).
[cited by applicant]
Hoyer, Katrina K, et al., “Interleukin-2 in the development and control of inflammatory disease”, Immunological Reviews, vol. 226, 2008, pp. 19-28 (10 pages).
[cited by applicant]
Humrich, Jens Y, et al., “Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus”, Proceedings of the National Academy of Sciences, vol. 107, No. 1, Jan. 5, 2010, pp. 204…
[cited by applicant]
Huston, James S, et al., “Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced in
[cited by applicant]
Imamichi, Hiromi , et al., “IL-15 acts as a potent inducer of CD4+CD25hi cells expressing FOXP3”, European Journal of Immunology, vol. 38, 2008, pp. 1621-1630, DOI: 10.1002/eji.200737607 (10 pages).
[cited by applicant]
Jazayeri, Jalal A, et al., “Fc-Based Cytokines: Prospects for Engineering Superior Therapeutics”, Biodrugs, vol. 22, No. 1, 2008, pp. 11-26 (16 pages).
[cited by applicant]
Koreth, John , et al., “Interleukin-2 and Regulatory T Cells in Graft-versus-Host Disease”, The New England Journal of Medicine, vol. 365, No. 22, Dec. 1, 2011, pp. 2055-2066, DOI: 10.1056/NEJMoa1108188 (12 pages).
[cited by applicant]
Lan, Ruth Y, et al., “The regulatory, inflammatory, and T cell programming roles of interleuking-2 (IL-2)”, Journal of Autoimmunity, vol. 31, 2008, pp. 7-12, DOI: 10.1016/j.jaut.2008.03.002 (6 pages).
[cited by applicant]
Leipe, Jan , et al., “Regulatory T cells in rheumatoid arthritis”, Arthritis Research & Therapy, vol. 7, Mar. 9, 2005, pp. 93-99, DOI: 10.1186/ar1718 (7 pages).
[cited by applicant]
Létourneau, Sven , et al., “IL-2- and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets”, J Allergy Clin Immunol, vol. 123, 2009, pp. 758-762, DOI: 10.1016/j.jaci.2009.02.011 (5 pages).
[cited by applicant]
Liston, Adrian , et al., “Tracing the action of IL-2 in tolerance to islet-specific antigen”, Immunology and Cell Biology, 2007, pp. 1-5 (5 pages).
[cited by applicant]
Liu, David V., et al., “Engineered Interleukin-2 Antagonists for the Inhibition of Regulatory T cells”, J Immunother, vol. 32, No. 9, 2009, pp. 887-894, DOI: 10.1097/CJI.0b013e3181b528da (17 pages).
[cited by applicant]
Liu, Hongyan , et al., “Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds”, Frontiers in Immunology, vol. 8, Article 38, Jan. 2017, pp. 1-15, DOI: 10.3389/fimmu.2017.00038 (15 pages).
[cited by applicant]
Lung-Chan, Mei , “Relationship between type I cytokine signaling and metamorphic effects: modeling of IL-21 receptor dynamics and prediction of IL-2 metamorphic regions”, China Outstanding Master's Degree Thesis, Full T…
[cited by applicant]
Malek, Thomas R, “The Biology of Interleukin-2”, Annual Review Immunol, vol. 26, 2008, pp. 456-479, DOI: 10.1146/annurev.immunol.26.021607.090357 (29 pages).
[cited by applicant]
Malek, Thomas R, et al., “Tolerance, Not Immunity, Crucially Depends on IL-2”, Nature Reviews: Immunology, vol. 4, Sep. 2004, pp. 665-674, DOI: 10.1038/nril435 (10 pages).
[cited by applicant]
Pandiyan, Pushpa , et al., “CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells”, Nature Immunology, vol. 8, No. 12, Dec. 2007, pp. 1353-1362, DOI: 10.1038/ni1536 (…
[cited by applicant]
Passerini, Laura , et al., “STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25− effector T cells”, International Immunology, vol. 20, No. 3, pp. 421-431, DOI: 10.1093…
[cited by applicant]
Peterson, Laurence B., et al., “A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease”, Journal of Autoimmunity, vol. 95, Dec. 2018, pp. 1-14, DOI: 10.101…
[cited by applicant]
Pilat, Nina , et al., “Treg-mediated prolonged survival of skin allografts without immunosuppression”, Proceedings of the National Academy of Sciences, vol. 116, No. 27, Jul. 2, 2019, pp. 13508-13516, DOI: 10.1073/pnas.…
[cited by applicant]
Ram, Ron , et al., “Pharmacologic prophylaxis regimens for acute graft-versus-host disease: past, present and future”, Leukemia & Lymphoma, vol. 54, No. 8, 2013, pp. 1591-1601, DOI: 10.3109/10428194.2012.762978.
[cited by applicant]
Rao, Balaji M, et al., “High-Affinity CD25-Binding IL-2 Mutants Potently Stimulate Persistent T Cell Growth”, Biochemistry, 2005, vol. 44, p. 10696-10701, DOI: 10.1021/bi050436x (6 pages).
[cited by applicant]
Rao, Balaji M, et al., “Interleukin-2 mutants with enhanced α-receptor subunit binding affinity”, Protein Engineering, vol. 16, No. 12, 2003, pp. 1081-1087, DOI: 10.1093/protein.gzg111 (7 pages).
[cited by applicant]
Rojas, Gertrudis , et al., “Directed evolution of super-secreted variants from phage-displayed human Interleukin-2”, Scientific Reports, vol. 9, No. 800, 2019, pp. 1-13, DOI: 10.1038/s41598-018-37280-5 (13 pages).
[cited by applicant]
Sakaguchi, Shimon , et al., “Regulatory T Cells and Immune Tolerance”, Cell, vol. 133, May 30, 2008, pp. 775-787, DOI: 10.1016/j.cell.2008.05.009 (13 pages).
[cited by applicant]
Shanafelt, Armen B, et al., “A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo”, Nature Biotechnology, vol. 18, Nov. 2000, pp. 1197-1202 (6 pages).
[cited by applicant]
Shevach, Ethan M, “Mechanisms of Foxp3+ T Regulatory Cell-Mediated Suppression”, Immunity, vol. 30, May 22, 2009, pp. 636-645, DOI: 10.1016/j.immuni.2009.04.010 (10 pages).
[cited by applicant]
Stauber, Deborah J, et al., “Crystal structure of the IL-2 signaling complex: Paradigm for a heterotrimeric cytokine receptor”, Proceedings of the National Academy of Sciences, vol. 103, No. 8, Feb. 21, 2006, pp. 2788-2…
[cited by applicant]
Sun, Wanping , et al., “A Novel Anti-Human Syndecan-1(CD138) Monoclonal Antibody 4B3: Characterization and Application”, Cellular & Molecular Immunology, vol. 4, No. 3, Jun. 2007, pp. 209-214 (6 pages).
[cited by applicant]
Tang, Qizhi , et al., “Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction”, Immunity, vol. 28, May 2008, pp. 687-697, DOI: 10.1016/j.immuni.2008.03.016 (22 pages).
[cited by applicant]
Tran, Dat Q, et al., “Induction of FOXP3 expression in naive human CD4+FOXP3− T cells by T-cell receptor stimulation is transforming growth factor-β-dependent but does not confer a regulatory phenotype”, Blood, vol. 110…
[cited by applicant]
Valencia, Xavier , et al., “CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases”, Nature Clinical Practice: Rheumatology, vol. 3, No. 11, Nov. 2007, pp. 619-626 (8 pages).
[cited by applicant]
Wang, Xinquan , et al., “Structure of the Quaternary Complex of Interleukin-2 with Its α, β, and γc Receptors”, Science, vol. 310, Nov. 18, 2005, pp. 1159-1163, DOI: 10.1126/science.1117893.
[cited by applicant]
Webster, Kylie E, et al., “In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression”, The Journal of Experimental Me…
[cited by applicant]
Wood , “Regulatory T Cells in Transplantation”, Transplant Proc, 2011, pp. 2135-2136.
[cited by applicant]
Yu, Tengteng , et al., “An Immune Based, Anti-CD138 Targeting Antibody for the Treatment of Multiple Myeloma”, Blood, vol. 132, Supp 1, Nov. 29, 2018, pp. 5617, DOI: 10.1182/blood-2018-99-119112, Abstract only, retrieve…
[cited by applicant]
Zeiser, Robert , et al., “Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells”, Blood, vol. 111, No. 1, Jan. 1, 2008, pp. 453-462…
[cited by applicant]
Zhao, Hong Liang , et al., “Increasing the homogeneity, stability and activity of human serum albumin and interferon-α2b fusion protein by linker engineering”, Protein Expression and Purification, vol. 61, 2008, pp. 73-…
[cited by applicant]
Zheng, Xin Xiao, et al., “The balance of deletion and regulation in allograft tolerance”, Immunological Reviews, vol. 196, 2003, pp. 75-84 (10 pages).
[cited by applicant]
Zorn, Emmanuel , et al., “IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo”, Blood, vol. 108, No. 5, Sep. 1, 2006,…
[cited by applicant]