Publications | spanglerlab

Leonard EK*, Tomala J*, Gould JR, Leff MI, Lin J-X, Li P, Porter MJ, Johansen ER, Thompson L, Cao SD, Hou S, Henclova T, Huliciak M, Sargunas PR, Fabilane CS, Vaněk O, Kovar M, Leonard WJ, Spangler JB. Engineered cytokine/antibody fusion proteins improve delivery of IL-2 to pro-inflammatory cells and promote antitumor activity. In Press, JCI Insight.

Berger S, Seeger F, Yu T-Y, Aydin M, Yang H, Rosenblum D, Guenin-Mace L, Glassman C, Arguinchona L, Sniezek C, Blackstone A, Carter L, Ravichandran R, Ahlrichs M, Murphy M, Swanson Pultz I, Kang A, Bera AK, Stewart L, Garcia KC, Naik S, Spangler JB, Beigel F, Siebeck M, Gropp R, Baker D. Pre-clinical proof of principle for orally delivered Th17 antagonist miniproteins. Cell. 2024. 187(16):4305-4317. PMID: 38936360.

Ray CMP, Yang H, Spangler JB, Mac Gabhann F. Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors. PLOS Comput Biol. 2024. 20(6):e1012157. PMID: 38848446.

Fabilane CS*, Stephenson AC*, Leonard EK, VanDyke D, Spangler JB. Cytokine/Antibody Fusion Protein Design and Evaluation. Curr Prot. 2024. 4(5):e1061. PMID: 38775006

Meksiriporn B, Spangler JB. Directed-evolution approach to empower EGFR targeting for immunotherapy. In press, Cell Rep Methods 2024. 4(4):100762. PMID: 38631347.

Ludwig SD, Meksiriporn B, Tan J, Kureshi R, Mishra A, Zhu A, Stavrakis G, Lee SJ, Schodt DJ, Wester MJ, Kumar D, Kaeo K, Lidke KA, Cox AL, Dooley H, Nimmagadda S, Spangler JB. Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1. Cell Chem Biol. 2024. 31(5):904-919.e11. PMID: 38547863.

Livingston NK, Hickey JW, Sim H Salathe SF, Choy J, Kong J, Silver AB, Stelzel JL, Omotoso MO, Li S, Chaisawangwong W, Roy S, Ariail EC, Lanis MR, Pradeep P, Bieler JG, Witte SE, Leonard E, Doloff JC, Spangler JB, Mao HQ, Schneck JP. In vivo stimulation of therapeutic antigen-specific t cells in an artificial lymph node matrix. In press, Adv Mater.

Fine J*, Meksiriporn B*, Tan J*, Spangler JB. Mechanism-driven design of multispecific antibodies for targeted disease treatment. In press, Annu Rev Chem Biomol Eng.

Tomala J, Cao SD, Spangler JB. Engineering anti-cytokine antibodies for immune modulation. J Immunol. 2024. 212(2):225-234. PMID: 38166248.

Tomasovic LM, Liu K, VanDyke D, Fabilane CS, Spangler JB. Molecular engineering of interleukin-2 for enhanced therapeutic activity in autoimmune diseases. Biodrugs. 2024. 38(2):227-248. PMID: 37999893.

Kishimoto TK, Max Fournier M, Alicia Michaud A, Gina Rizzo G, Roy C, Capela T, Nukolova N, Li N, Doyle L, Fu F, VanDyke D, Traber PG, Spangler JB, Leung SS, Ilyinskii PO. Rapamycin nanoparticles increase the therapeutic window of engineered interleukin-2 and drive expansion of antigen-specific regulatory T cells for protection against autoimmune disease. In press, J Autoimmun.

VanDyke D, Xu L, Gilbreth RN, Baca M, Gao C, Hunt J, Spangler JB. Redirecting the specificity of tripartite motif containing-21 scaffolds using a novel discovery and design approach. 2023. J Biol Chem. 299(12):105381. PMID: 37866632.

Silver AB, Tzeng SY, Lager M, Wang J, Ishihara J, Green JJ, Spangler JB. An engineered collagen-binding cytokine/antibody fusion protein improves the intratumoral bioavailability, tolerability, and therapeutic efficacy of interleukin-2. 2023. Cell Rep Med. 4(11): 101289. PMID: 37992685.

Dykema AG*, Zhang J*, Cheung LS, Cherry CM, Caushi JX, Nishimoto M, Conner S, Zhang B, Li T, Munoz AJ, Singh D, Rashid R, Helms R, Mitchell-Flack M, Bom S, Tam A, Nick N, Sawosik CA, Tirado LE, Tomasovic LM, VanDyke D, Spangler JB, Anagnostou V, Yang S, Taube J, Brahmer JR, Forde PM, Yegnasubramanian S, Ji H†, Pardoll DM†, Smith KN†. Lung tumor-infiltrating Treg subsets have divergent transcriptional profiles and function linked to checkpoint blockade response. 2023. Sci Immunol. 8(87):eadg1487. PMID: 37713507.

Sun H, Lee H, Kim S, Gingras AR, Du Q, McLaughlin W, Ablack J, Lopez-Ramirez MA, Lagarrigue F, Fan Z, Chang JT, VanDyke D, Spangler JB, Ginsberg M. IL-2 can signal via chemokine receptors to promote regulatory T cells' suppressive function. 2023. Cell Rep. 42(8):112996. PMID: 37598341.

Bernstein ZJ, Shenoy A, Chen A, Heller NM†, Spangler JB†. Engineering the IL-4/IL-13 axis for targeted immune modulation. Immunol Rev. 2023. 320(1):29-57. PMID: 37283511.

Rhodes KR, Tzeng SY, Iglesias M, Lee D, Storm K, Neshat SY, VanDyke D, Spangler JB, Raimondi G†, Green JJ†. Bioengineered tolerogenic degradable microparticles expand myelin- specific regulatory t cells and therapeutically reverse autoreactivity in a mouse model of multiple sclerosis. 2023. Sci Adv. 9(22):eadd8693. PMID: 37267370.

Silver AB, Wang J, Spangler JB. Masking T-cell engagers mitigates on-target off-tumor activity. 2023. Nat Cancer. 4(4):439-441. PMID: 36997746.

Yang H*, Ulge UY*, Quijano-Rubio A*, Bernstein ZJ*, Maestas, Jr. DR, Chun J, Wang W, Lin J-X, Jude KM, Singh S, Orcutt-Jahns BT, Li P, Mou J, Chung L, Kuo Y-H, Ali YH, Meyer AS, Grayson WL, Heller NM, Garcia KC, Leonard WJ, Silva D-A, Elisseeff JH, Baker D†, Spangler JB†. Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo cytokine scaffolds. 2023. Nat Chem Biol. 19(9):1127-1137. PMID: 37024727.

Kizerwetter M, Pietz K, Tomasovic LM, Spangler JB. Empowering gene delivery with protein engineering platforms. 2023. Gene Ther. 30:775-782. PMID: 36529795.

Deckers J*, Anbergen T*, Hokke AM*, de Bruin K, de Dreu A, Schrijver DP, Toner YC, Beldman TJ, Spangler JB, de Greef TFA, Grisoni F, van der Meel R, Joosten LAB, Merkx M, Mulder WJ, Netea MG. Engineering cytokine therapeutics. 2023. Nat Rev Bioeng. 1(4):286-303. PMID: 37064653.

Quijano-Rubio A, Bhuiyan AM, Yang H, Leung I, Bello E, Ali LR, Zhangxu K, Wang W, Lajoie M, Rashmi Ravichandran R, Kuo Y-H, Dougan SK, Riddell SR, Spangler JB†, Dougan M†, Silva DA†, Baker D†. Conditionally active de novo IL-2/IL-15 mimetics for targeted immunotherapy. 2023. Nat Biotechnol. 41(4):532-540. PMID: 36316485.

Krohl PJ, Fine J, VanDyke D, Ang Z, Kim KB, Thomas-Tikhonenko A, Spangler JB. Discovery of antibodies targeting multipass transmembrane proteins using a suspension cell-based evolutionary approach. 2023. Cell Rep Methods. 3(3):100429. PMID: 37056366.

Anderson CF, Wang Q, Stern D, Leonard EK, Sun B, Fergie KJ, Choi C, Spangler JB, Villano J, Pekosz A, Brayton CF, Jia H, Cui H. Supramolecular filaments for concurrent ACE2 docking and enzymatic activity silencing enable coronavirus capture and infection prevention. 2023. Matter. 583-604. PMID: 36531610.

Bokhari RS, Beheshti A, Blutt SE, Bowles DE, Britton R, Bronner M, Chatterjee A, Clay DE, Courtney C, Fox D, Gerecht S, Grabham P, Jezuit EA, Kirsch DG, Maletic-Savatic M, Miller KM, Montague RA, Nagpal P, Pierce NA, Porada C, Rosenberg SM, Sargunas P, Sharma S, Spangler J, Thomas D, Weil MM, Whitcomb L, Cao X, Donoviel D. Looking on the horizon: Potential and unique approaches to developing radiation countermeasures for deep space travel. 2022. Life Sci Space Res. 35:105-112. PMID: 36336356.

VanDyke D, Taylor JD, Kaeo KJ, Hunt J, Spangler JB. Biologics-based degraders – an expanding toolkit for targeted protein degradation. 2022. Curr Opin Biotechnol. 78:102807. PMID: 36179405.

Yang H*, Karl MN*, Wang W, Starich B, Tan H, Kiemen A, Pucsek AB, Kuo YH, Russo GC, Pan T, Jaffee EM, Fertig EJ, Wirtz D, Spangler JB. Engineered bispecific antibodies targeting the interleukin-6 and -8 receptors potently inhibit cancer cell migration and tumor metastasis. 2022. Mol Ther. 30(11):3430-3449. PMID: 35841152.

VanDyke D, Iglesias M, Tomala J, Young A, Smith J, Perry JA, Gebara E, Cross AR, Cheung LS, Dykema AG, Orcutt-Jahns BT, Henclová T, Golias J, Balolong J, Tomasovic LM, Funda D, Meyer AS, Pardoll DM, Hester J, Issa F, Hunter CA, Anderson MS, Bluestone JA, Raimondi G, Spangler JB. Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection. 2022. Cell Rep. 41(3):111478. PMID: 36261022.

Isser A, Silver AB, Pruitt HC, Mass M, Elias EH, Aihara G, Kang S-S, Bachmann N, Chen Y-Y, Leonard EK, Bieler JG, Chaisawangwong W, Choy J, Shannon SR, Gerecht S, Weber JS, Spangler JB, Schneck JP. A Nanoparticle Platform Mobilizes CD4+ T Cells for Immunotherapy. 2022. Nat Commun. 13(1):6086. PMID: 36241639.

VanDyke D, Taylor JD, Kaeo KJ, Hunt J, Spangler JB. Biologics-based degraders – an expanding toolkit for targeted protein degradation. In press, Curr Opin Biotechnol.

Luly KM, Lee SJ, Yang H, Wang W, Ludwig SD, Tarbox HE, Wilson DR, Green JJ†, Spangler JB†. Poly(beta-amino ester)s as high-yield transfection reagents for recombinant protein production. 2022. Int J Nanomedicine. 17:4469-4479. PMID: 36176585.

Ludwig SD*, Bernstein ZJ*, Agatemor C, Dammen-Brower K, Ruffolo J, Rosas JM, Post JD, Cole RN, Yarema KJ, Spangler JB. A versatile design platform for glycoengineering therapeutic antibodies. MAbs. 14(1):2095704. PMID: 35815437.

Sargunas PR, Spangler JB. Joined at the hip: The role of complementarity-determining region in antibody self-association. 2022. Proc Natl Acad Sci U S A. 119(28)e2208330119. PMID: 35776537.

Leonard EK*, Pellitero MA*, Juelg B, Spangler JB†, Arroyo-Currás N†. Antibody-invertase fusion protein enables quantitiative detection of SARS-CoV-2 antibodies using widely available glucometers. J Am Chem Soc. 2022. 144(25):11226-11237. PMID: 35675509.

de Rutte J, Dimatteo R, Archang MM, van Zee M; Koo D, Lee S; Sharrow AC, Krohl PJ, Mellody M, Zhu S, Eichenbaum JV, Kizerwetter M, Udani S, Ha K, Willson RC, Bertozzi AL, Spangler JB, Damoiseaux R, Di Carlo D. Suspendable hydrogel nanovials for massively parallel single-cell functional analysis and sorting. ACS Nano. 2022. 16(5):7242-7257. PMID: 35324146.

Casciola-Rosen L, Thiemann DR, Andrade F, Trejo Zambrano MI, Leonard EK, Spangler JB, Skinner N, Bailey J, Yegnasubramanian S, Wang R, Vaghasia A, Gupta A, Cox AL, Ray SC, Linville RM, Guo Z, Searson PC, Machamer CE, Desiderio S, Sauer L, Laeyendecker O, Garibaldi BT, Gao L, Damarla M, Hassoun P, Hooper JE, Mecoli CE, Christopher-Stine L, Gutierrez-Alamillo L, Yang Q, Hines D, Clarke WA, Rothman R, Pekosz A, Fenstermacher KJ, Wang Z, Zeger SL, Rosen A. IgM anti-ACE2 autoantibodies in severe COVID-19 activate complement and perturb vascular endothelial function. JCI Insight. 2022. 7(9):e158362. PMID: 35349483.

Dammen-Brower K, Epler P, Zhu S, Bernstein ZJ, Stabach PR, Braddock DT, Spangler JB, & Yarema KJ. Strategies for glycoengineering therapeutic proteins. Front Chem. 2022. 10:863118. PMID: 35494652.

Silver AB, Leonard EK, Gould JR, Spangler JB. Engineered antibody fusion proteins for targeted disease therapy. Trends Pharmacol. Sci. 2021. 42(12):1064-1081. PMID: 34706833.

Bernstein ZJ, Spangler JB. Insights into the anticancer mechanisms of interleukin-15 from engineered cytokine therapies. J Clin Invest. 2021. 131(19):e152857. PMID: 34596048.

Kumar D, Mishra A, Lisok A, Kureshi R, Shelake S, Plyku D, Sen R, Doucet M, Desilva R, Mease R, Ford PM, Jaffee EM, Desai P, Ganguly S, Gabrielson E, Vaidya D, Spangler JB, Nimmagadda S. Pharmacodynamic measures within tumor exposes differential activity of PD(L)-1 antibody therapeutics. Proc Natl Acad Sci U S A. 2021. 118(37):e2107982118. PMID: 34508005.

Sargunas PR, Spangler JB. Full speed AHEAD in antibody discovery. Nat Chem Biol. 2021. 17(10):1011-1012. PMID: 34211163.

Glassman CR, Mathiharan YK, Jude KM, Su L, Panova O, Lupardus PJ, Spangler JB, Ely LK, Thomas C, Skiniotis G, Garcia KC. Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. Cell. 2021; 184(4):983-99. PMID: 33606986.

Yang H, Kuo Y, Smith ZI, Spangler JB. Targeting cancer metastasis with antibody therapeutics. Wiley Interdiscip Rev Nanomed Nanobi. 2021; e1698. PMID: 33463090.

Krohl PJ, Kim KB, Lew L, VanDyke D, Ludwig SD, Spangler JB. A suspension cell-based interaction platform for interrogation of membrane proteins. AIChE J. 2020; 66(12):e16995. Featured on the cover.

Kureshi R, Zhu A, Shen J, Tzeng SY, Astrab LR, Sargunas PR, Green JJ, Campochiaro PA, Spangler JB. Structure-guided molecular engineering of a vascular endothelial growth factor antagonist to treat retinal diseases. Cell Mol Bioeng. 2020; 13(5):405-418 PMID: 33184574.

VanDyke D, Wang W, Spangler JB. Innovative synthetic signaling technologies for immunotherapy. Curr Opin Biomed Eng. 2020; 16:1-8.

Yang H, Kureshi R, Spangler JB. Structural basis for signaling through shared common g chain cytokines, In: Structural immunology. Jin T & Yin Q ed. 2020; Springer Nature.

Tomala J, Spangler JB. Characterization of immune cell subset expansion in response to therapeutic treatment in mice, In: Methods Mol Biol 2111. Liu C ed. 2020; Humana Press.

Spangler JB*, Moraga I*, Jude KM, Savvides CS, Garcia KC. A strategy for the selection of monovalent antibodies that span protein dimer interfaces. J Biol Chem. 2019; 294(38):13876-86. PMID 31387945.

Leonard EK, Leff MI, Spangler JB. Weaponizing T-cell receptors through molecular engineering. J Biol Chem. 2019; 294(15):5805-6. PMID 30979848.

Krohl PJ, Ludwig SD, Spangler JB. Emerging technologies in protein interface engineering for biomedical applications. Curr Opin Biotechnol. 2019; 60:82-8. PMID 30802788.

Silva DA*, Yu S*, Ulge U*, Spangler JB*, Jude KM, Labão- Almeida C, Ali L, Quijano-Rubio A, Ruterbusch M, Leung I, Biary T, Crowley SJ, Marcos E, Walkey CD, Weitzner BD, Pardo-Avila F, Castellanos J, Carter L, Stewart L, Riddell SR, Pepper M, Bernardes GJL, Dougan M, Garcia KC, Baker D. De novo design of potent and selective mimics of IL-2/IL-15. Nature. 2019; 565(7738):186-91. PMID: 30626941.

Spangler JB, Trotta E, Tomala J, Peck A, Young TA, Savvides CS, Silveria S, Votavova P, Salafsky J, Pande VS, Kovar M, Bluestone JA, Garcia KC. Engineering a single-agent cytokine/antibody fusion that selectively expands regulatory T cells for autoimmune disease therapy. J Immunol. 2018; 201(7)2094-106. PMCID: 6173196.

Kureshi R, Bahri M, Spangler JB. Reprogramming immune proteins as therapeutics using molecular engineering. Curr Opin Chem Eng. 2018;19:27-34.

Moraga, I*, Spangler JB*, Menoza JL*, Gakovic M, Wehrman TS, Krutzik P, Garcia KC. Synthekines are surrogate cytokine and growth factor agonists that compel signaling through non-natural receptor dimers. eLife. 2017;6:e22882. PMID: 28498099.

Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC. Antibodies to interleukin-2 elicit selective T cell subset potentiation through distinct conformational mechanisms. Immunity. 2015;42(5):815-25. PMCID: 4439582.

Mitra S, Ring AM, Amarnath S, Spangler JB, Li P, Ju W, Fischer S, Oh J, Spolski R, Weiskopf K, Kohrt H, Foley JE, Rajagopalan S, Long EO, Fowler DH, Waldmann TA, Garcia KC, Leonard WJ. Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps. Immunity. 2015;42(5):826-38. PMCID: 4560365.

Spangler JB, Moraga I, Mendoza JL, Garcia KC. Insights into cytokine-receptor interactions from cytokine engineering. Annu Rev Immunol. 2015;33:139-67. PMCID: 4445396.

Moraga I, Spangler J, Mendoza JL, Garcia KC. Multifarious determinants of cytokine receptor signaling specificity. Adv Immunol. 2014;121:1-39. PMCID: 4449261.

Spangler JB, Manzari MT, Rosalia EK, Chen TF, Wittrup KD. Triepitopic antibody fusions inhibit cetuximab-resistant BRAF and KRAS mutant tumors via EGFR signal repression. J Mol Biol. 2012;422(4):532-44. PMCID: 4041985.

Spangler JB, Neil JR, Abramovitch S, Yarden Y, White FM, Lauffenburger DA, Wittrup KD. Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling. Proc Natl Acad Sci U S A. 2010;107(30):13252-7. PMCID: 2922117.

You M*, Spangler J*, Li E, Han X, Ghosh P, Hristova K. Effect of pathogenic cysteine mutations on FGFR3 transmembrane domain dimerization in detergents and lipid bilayers. Biochemistry. 2007;46(39):11039-46. PMID: 17845056.

Iwamoto T, You M, Li E, Spangler J, Tomich JM, Hristova K. Synthesis and initial characterization of FGFR3 transmembrane domain: consequences of sequence modifications. Biochim Biophys Acta. 2005;1668(2):240-7. PMID: 15737335.

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