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Targeting Activated Macrophages Via a Functional Folate Receptor for Potential Treatment of Autoimmune/Inflammatory Disorders

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Targeted Drug Strategies for Cancer and Inflammation

Abstract

The folate receptor expressed by activated macrophages associated with chronic inflammation is fully functional in binding/internalization of high-affinity folate ligands. The recent effort in developing folate-targeted anti-macrophage therapies has yielded some encouraging results. However, the challenges lie not so much in finding the right ligand, but rather its multifaceted nature in identifying suitable intracellular targets, finding highly potent base drugs, design of appropriate linker chemistry, and choosing “realistic” inflammation models to demonstrate efficacy and target specificity. In this chapter we will provide background for this complex topic and discuss the rationale for finding a balance in these specific areas of interest.

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References

  • Adcock IM (2007) HDAC inhibitors as anti-inflammatory agents. Br J Pharmacol 150:829–831

    Article  PubMed  CAS  Google Scholar 

  • Antoni C, Kalden JR (1999) Combination therapy of the chimeric monoclonal anti-tumor necrosis factor alpha antibody (infliximab) with methotrexate in patients with rheumatoid arthritis. Clin Exp Rheumatol 17:S73–S77

    PubMed  CAS  Google Scholar 

  • Assi K, Pillai R, Gomez-Munoz A et al (2006) The specific JNK inhibitor SP600125 targets tumour necrosis factor-alpha production and epithelial cell apoptosis in acute murine colitis. Immunology 118:112–121

    Article  PubMed  CAS  Google Scholar 

  • Atzeni F, Doria A, Carrabba M et al (2007) Potential target of infliximab in autoimmune and inflammatory diseases. Autoimmun Rev 6:529–536

    Article  PubMed  CAS  Google Scholar 

  • Barnette MS, Christensen SB, Essayan DM et al (1998) SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: in vitro anti-inflammatory actions. J Pharmacol Exp Ther 284:420–426

    PubMed  CAS  Google Scholar 

  • Baslund B, Gregers J, Nielsen CH (2008) Reduced folate carrier polymorphism determines methotrexate uptake by B cells and CD4+ T cells. Rheumatology (Oxford) 47:451–453

    Article  CAS  Google Scholar 

  • Baumer W, Hoppmann J, Rundfeldt C et al (2007) Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets 6:17–26

    Article  PubMed  Google Scholar 

  • Bleesing J, Prada A, Siegel DM et al (2007) The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum 56:965–971

    Article  PubMed  CAS  Google Scholar 

  • Bourlier V, Bouloumie A (2009) Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes Metab 35:251–260

    Article  PubMed  CAS  Google Scholar 

  • Braccini L, Morello F, Perino A et al (2009) Post-Wortmannin era: novel phosphoinositide 3-kinase inhibitors with potential therapeutic applications. Curr Enzyme Inhib 5(12):66–86

    CAS  Google Scholar 

  • Bresnihan B, Gerlag DM, Rooney T et al (2007) Synovial macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers. J Rheumatol 34:620–622

    PubMed  Google Scholar 

  • Bruyn GA, Tate G, Caeiro F et al (2008) Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study. Ann Rheum Dis 67:1090–1095

    Article  PubMed  CAS  Google Scholar 

  • Chan J, Leenen PJ, Bertoncello I et al (1998) Macrophage lineage cells in inflammation: characterization by colony-stimulating factor-1 (CSF-1) receptor (c-Fms), ER-MP58, and ER-MP20 (Ly-6C) expression. Blood 92:1423–1431

    PubMed  CAS  Google Scholar 

  • Clark RA, Kupper TS (2006) Misbehaving macrophages in the pathogenesis of psoriasis. J Clin Invest 116:2084–2087

    Article  PubMed  CAS  Google Scholar 

  • Cronstein BN (2005) Low-dose methotrexate: a mainstay in the treatment of rheumatoid arthritis. Pharmacol Rev 57:163–172

    Article  PubMed  CAS  Google Scholar 

  • Demetter P, De Vos M, Van Huysse JA et al (2005) Colon mucosa of patients both with spondyloarthritis and Crohn’s disease is enriched with macrophages expressing the scavenger receptor CD163. Ann Rheum Dis 64:321–324

    Article  PubMed  CAS  Google Scholar 

  • Drexler SK, Kong PL, Wales J et al (2008) Cell signalling in macrophages, the principal innate immune effector cells of rheumatoid arthritis. Arthritis Res Ther 10:216. doi:10.1186/ar2481

    Article  PubMed  Google Scholar 

  • Fisher RE, Siegel BA, Edell SL et al (2008) Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors. J Nucl Med 49:899–906

    Article  PubMed  Google Scholar 

  • Fong CH, Bebien M, Didierlaurent A et al (2008) An antiinflammatory role for IKKbeta through the inhibition of “classical” macrophage activation. J Exp Med 205:1269–1276

    Article  PubMed  CAS  Google Scholar 

  • Fougerat A, Gayral S, Gourdy P et al (2008) Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes. Circulation 117:1310–1317

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4:281–286

    Article  PubMed  CAS  Google Scholar 

  • Gibbs DD, Theti DS, Wood N et al (2005) BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res 65:11721–11728

    Article  PubMed  CAS  Google Scholar 

  • Gillooly K, Pattoli M, Taylor T et al (2009) Periodic, partial inhibition of IKK{beta}-mediated signaling yields therapeutic benefit in preclinical models of rheumatoid arthritis. J Pharmacol Exp Ther 331:349–360

    Article  PubMed  CAS  Google Scholar 

  • Guay D, Boulet L, Friesen RW et al (2008) Optimization and structure-activity relationship of a series of 1-phenyl-1, 8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent and effective PDE4 inhibitor. Bioorg Med Chem Lett 18:5554–5558

    Article  PubMed  CAS  Google Scholar 

  • Halili MA, Andrews MR, Sweet MJ et al (2009) Histone deacetylase inhibitors in inflammatory disease. Curr Top Med Chem 9:309–319

    Article  PubMed  CAS  Google Scholar 

  • Hall MJ, Lawrence DA, Lansiedel JC et al (1997) Long-term exposure to methotrexate induces immunophenotypic changes, decreased methotrexate uptake and increased dihydrofolate gene copy number in Jurkat T cells. Int J Immunopharmacol 19:709–720

    Article  PubMed  CAS  Google Scholar 

  • Hamilton JA, Tak PP (2009) The dynamics of macrophage lineage populations in inflammatory and autoimmune diseases. Arthritis Rheum 60:1210–1221

    Article  PubMed  Google Scholar 

  • Haringman JJ, Gerlag DM, Zwinderman AH et al (2005) Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 64:834–838

    Article  PubMed  CAS  Google Scholar 

  • Hope HR, Anderson GD, Burnette BL et al (2009) Anti-inflammatory properties of a novel N-phenyl pyridinone inhibitor of p38 MAP kinase: preclinical to clinical translation. J Pharmacol Exp Ther 331:882–895

    Article  PubMed  CAS  Google Scholar 

  • Huang QQ, Sobkoviak R, Jockheck-Clark AR et al (2009) Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J Immunol 182:4965–4973

    Article  PubMed  CAS  Google Scholar 

  • Jackman AL, Theti DS, Gibbs DD (2004) Antifolates targeted specifically to the folate receptor. Adv Drug Deliv Rev 56:1111–1125

    Article  PubMed  CAS  Google Scholar 

  • Johnson WJ, DiMartino MJ, Hanna N (1986) Macrophage activation in rat models of inflammation and arthritis: determination of markers of stages of activation. Cell Immunol 103:54–64

    Article  PubMed  CAS  Google Scholar 

  • Kamen BA, Capdevila A (1986) Receptor-mediated folate accumulation is regulated by the cellular folate content. Proc Natl Acad Sci USA 83:5983–5987

    Article  PubMed  CAS  Google Scholar 

  • Katsiari CG, Liossis SN, Sfikakis PP (2010) The pathophysiologic role of monocytes and macrophages in systemic lupus erythematosus: a reappraisal. Semin Arthritis Rheum 39:491–503

    Article  PubMed  CAS  Google Scholar 

  • Kinne RW, Brauer R, Stuhlmuller B et al (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2:189–202

    Article  PubMed  CAS  Google Scholar 

  • Kinne RW, Stuhlmuller B, Burmester GR (2007) Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res Ther 9:224. doi:10.1186/ar2333

    Article  PubMed  Google Scholar 

  • Leamon CP, Jackman AL (2008) Exploitation of the folate receptor in the management of cancer and inflammatory disease. Vitam Horm 79:203–233

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Low PS (1991) Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. Proc Natl Acad Sci USA 88:5572–5576

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Parker MA (2006) Vitamin-targeted imaging agents. US patent 7128893, 31 Oct 2006

    Google Scholar 

  • Leamon CP, Parker MA, Vlahov IR et al (2002) Synthesis and biological evaluation of EC20: a new folate-derived, (99m)Tc-based radiopharmaceutical. Bioconjug Chem 13:1200–1210

    Article  PubMed  CAS  Google Scholar 

  • Leamon CP, Reddy JA, Vlahov IR et al (2007) Preclinical antitumor activity of a novel folate-targeted dual drug conjugate. Mol Pharm 4:659–667

    Article  PubMed  CAS  Google Scholar 

  • Lin HS, Hu CY, Chan HY et al (2007) Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br J Pharmacol 150:862–872

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Low PS (2002) Folate targeting of haptens to cancer cell surfaces mediates immunotherapy of syngeneic murine tumors. Cancer Immunol Immunother 51:153–162

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Sega E, Low PS (2005) Folate receptor-targeted immunotherapy: induction of humoral and cellular immunity against hapten-decorated cancer cells. Int J Cancer 116:710–719

    Article  PubMed  CAS  Google Scholar 

  • Lu Y, Xu LC, Parker N et al (2006) Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a folate-hapten conjugate-targeted immunotherapy in hapten-immunized mice. Mol Cancer Ther 5:3258–3267

    Article  PubMed  CAS  Google Scholar 

  • Mantadakis E, Cole PD, Kamen BA (2005) High-dose methotrexate in acute lymphoblastic leukemia: where is the evidence for its continued use? Pharmacotherapy 25:748–755

    Article  PubMed  CAS  Google Scholar 

  • Matteson EL, Lowe VJ, Prendergast FG et al (2009) Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan. Clin Exp Rheumatol 27:253–259

    PubMed  CAS  Google Scholar 

  • Mbalaviele G, Sommers CD, Bonar SL et al (2009) A novel, highly selective, tight binding IkappaB kinase-2 (IKK-2) inhibitor: a tool to correlate IKK-2 activity to the fate and functions of the components of the nuclear factor-kappaB pathway in arthritis-relevant cells and animal models. J Pharmacol Exp Ther 329:14–25

    Article  PubMed  CAS  Google Scholar 

  • McGuire JJ, Haile WH (2009) Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5, 8, 10-trideazapteroyl-d, l-4′-methyleneglutamic acid (CH-1504) and its analogs. Biochem Pharmacol 77:1161–1172

    Article  PubMed  CAS  Google Scholar 

  • Monneaux F, Muller S (2009) Molecular therapies for systemic lupus erythematosus: clinical trials and future prospects. Arthritis Res Ther 11:234. doi:10.1186/ar2711

    Article  PubMed  Google Scholar 

  • Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    Article  PubMed  CAS  Google Scholar 

  • Nagai T, Tanaka M, Tsuneyoshi Y et al (2006) In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells. Arthritis Rheum 54:3126–3134

    Article  PubMed  CAS  Google Scholar 

  • Nagayoshi R, Nakamura M, Ijiri K et al (2003) LY309887, antifolate via the folate receptor suppresses murine type II collagen-induced arthritis. Clin Exp Rheumatol 21:719–725

    PubMed  CAS  Google Scholar 

  • Nagayoshi R, Nagai T, Matsushita K et al (2005) Effectiveness of anti-folate receptor beta antibody conjugated with truncated Pseudomonas exotoxin in the targeting of rheumatoid arthritis synovial macrophages. Arthritis Rheum 52:2666–2675

    Article  PubMed  CAS  Google Scholar 

  • Nakashima-Matsushita N, Homma T, Yu S et al (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616

    Article  PubMed  CAS  Google Scholar 

  • Neta R, Oppenheim JJ (2001) Physiology of inflammation. J Leukoc Biol 69:850

    CAS  Google Scholar 

  • Nguyen GC, Harris ML, Dassopoulos T (2006) Insights in immunomodulatory therapies for ulcerative colitis and Crohn’s disease. Curr Gastroenterol Rep 8:499–505

    Article  PubMed  Google Scholar 

  • Oerlemans R, van der Heijden J, Vink J et al (2006) Acquired resistance to chloroquine in human CEM T cells is mediated by multidrug resistance-associated protein 1 and provokes high levels of cross-resistance to glucocorticoids. Arthritis Rheum 54:557–568

    Article  PubMed  CAS  Google Scholar 

  • Ohori M (2008) ERK inhibitors as a potential new therapy for rheumatoid arthritis. Drug News Perspect 21:245–250

    Article  PubMed  CAS  Google Scholar 

  • Palombella VJ, Conner EM, Fuseler JW et al (1998) Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis. Proc Natl Acad Sci USA 95:15671–15676

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Turk MJ, Breur GJ et al (2004a) Folate receptor-mediated targeting of therapeutic and imaging agents to activated macrophages in rheumatoid arthritis. Adv Drug Deliv Rev 56:1205–1217

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Reddy JA, Leamon CP et al (2004b) Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery. Mol Pharmacol 66:1406–1414

    Article  PubMed  CAS  Google Scholar 

  • Paulos CM, Varghese B, Widmer WR et al (2006) Folate-targeted immunotherapy effectively treats established adjuvant and collagen-induced arthritis. Arthritis Res Ther 8:R77. doi:10.1186/ar1944

    Article  PubMed  Google Scholar 

  • Qureshi N, Vogel SN, Van Way C III et al (2005) The proteasome: a central regulator of inflammation and macrophage function. Immunol Res 31:243–260

    Article  PubMed  CAS  Google Scholar 

  • Ranganathan P, Culverhouse R, Marsh S et al (2008) Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in Caucasian and African American patients with rheumatoid arthritis. J Rheumatol 35:572–579

    PubMed  CAS  Google Scholar 

  • Reddy JA, Dorton R, Westrick E et al (2007) Preclinical evaluation of EC145, a folate-vinca alkaloid conjugate. Cancer Res 67:4434–4442

    Article  PubMed  CAS  Google Scholar 

  • Rice JW, Veal JM, Fadden RP et al (2008) Small molecule inhibitors of Hsp90 potently affect inflammatory disease pathways and exhibit activity in models of rheumatoid arthritis. Arthritis Rheum 58:3765–3775

    Article  PubMed  CAS  Google Scholar 

  • Ross JF, Wang H, Behm FG et al (1999) Folate receptor type beta is a neutrophilic lineage marker and is differentially expressed in myeloid leukemia. Cancer 85:348–357

    Article  PubMed  CAS  Google Scholar 

  • Schindler JF, Monahan JB, Smith WG (2007) p38 pathway kinases as anti-inflammatory drug targets. J Dent Res 86:800–811

    Article  PubMed  CAS  Google Scholar 

  • Shen F, Ross JF, Wang X et al (1994) Identification of a novel folate receptor, a truncated receptor, and receptor type beta in hematopoietic cells: cDNA cloning, expression, immunoreactivity, and tissue specificity. Biochemistry 33:1209–1215

    Article  PubMed  CAS  Google Scholar 

  • Simmonds RE, Foxwell BM (2008) Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Rheumatology (Oxford) 47:584–590

    Article  CAS  Google Scholar 

  • Späh F (2008) Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. Br J Dermatol 159:10–17

    Article  PubMed  Google Scholar 

  • Strnad J, Burke JR (2007) IkappaB kinase inhibitors for treating autoimmune and inflammatory disorders: potential and challenges. Trends Pharmacol Sci 28:142–148

    Article  PubMed  CAS  Google Scholar 

  • Szekanecz Z, Koch AE (2007) Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol 19:289–295

    Article  PubMed  Google Scholar 

  • Szekanecz Z, Koch AE (2008) Vascular involvement in rheumatic diseases: “vascular rheumatology”. Arthritis Res Ther 10:224. doi:10.1186/ar2515

    Article  PubMed  Google Scholar 

  • Tas SW, Remans PH, Reedquist KA et al (2005) Signal transduction pathways and transcription factors as therapeutic targets in inflammatory disease: towards innovative antirheumatic therapy. Curr Pharm Des 11:581–611

    Article  PubMed  CAS  Google Scholar 

  • Teachey DT, Greiner R, Seif A et al (2009) Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol 145:101–106

    Article  PubMed  CAS  Google Scholar 

  • Thalhamer T, McGrath MA, Harnett MM (2008) MAPKs and their relevance to arthritis and inflammation. Rheumatology (Oxford) 47:409–414

    Article  CAS  Google Scholar 

  • Turk MJ, Breur GJ, Widmer WR et al (2002) Folate-targeted imaging of activated macrophages in rats with adjuvant-induced arthritis. Arthritis Rheum 46:1947–1955

    Article  PubMed  Google Scholar 

  • van der Heijden JW, Dijkmans BA, Scheper RJ et al (2007) Drug insight: resistance to methotrexate and other disease-modifying antirheumatic drugs – from bench to bedside. Nat Clin Pract Rheumatol 3:26–34

    Article  PubMed  Google Scholar 

  • van der Heijden JW, Oerlemans R, Dijkmans BA et al (2009a) Folate receptor beta as a potential delivery route for novel folate antagonists to macrophages in the synovial tissue of rheumatoid arthritis patients. Arthritis Rheum 60:12–21

    Article  PubMed  Google Scholar 

  • van der Heijden JW, Oerlemans R, Tak PP et al (2009b) Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide. Arthritis Rheum 60:669–677

    Article  PubMed  Google Scholar 

  • Varatharajan N, Lim IG, Anandacoomarasamy A et al (2009) Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice. Intern Med J 39:228–236

    Article  PubMed  CAS  Google Scholar 

  • Varghese B, Haase N, Low PS (2007) Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and prolonged survival in two murine models of systemic lupus erythematosus. Mol Pharm 4:679–685

    Article  PubMed  CAS  Google Scholar 

  • Vlahov IR, Santhapuram HK, Kleindl PJ et al (2006) Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part 1: EC145, a folic acid conjugate of desacetylvinblastine monohydrazide. Bioorg Med Chem Lett 16:5093–5096

    Article  PubMed  CAS  Google Scholar 

  • Waldburger JM, Firestein GS (2009) Garden of therapeutic delights: new targets in rheumatic diseases. Arthritis Res Ther 11:206

    Article  PubMed  Google Scholar 

  • Wessels JA, de Vries-Bouwstra JK, Heijmans BT et al (2006) Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum 54:1087–1095

    Article  PubMed  CAS  Google Scholar 

  • Westerhof GR, Schornagel JH, Kathmann I et al (1995) Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: correlates of molecular-structure and biological activity. Mol Pharmacol 48:459–471

    PubMed  CAS  Google Scholar 

  • Williams RO (2004) Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med 98:207–216

    PubMed  CAS  Google Scholar 

  • Wilson HM, Barker RN, Erwig LP (2009) Macrophages: promising targets for the treatment of atherosclerosis. Curr Vasc Pharmacol 7:234–243

    Article  PubMed  CAS  Google Scholar 

  • Winkler J, Wright D, Pheneger J et al (2009) ARRY-162, a potent and selective inhibitor of Mek 1/2: preclinical and clinical evidence of activity in arthritis. Proceeding of 9th World congress on inflammation

    Google Scholar 

  • Xaus J, Comalada M, Valledor AF et al (2001) Molecular mechanisms involved in macrophage survival, proliferation, activation or apoptosis. Immunobiology 204:543–550

    Article  PubMed  CAS  Google Scholar 

  • Xia W, Hilgenbrink AR, Matteson EL et al (2009) A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood 113:438–446

    Article  PubMed  CAS  Google Scholar 

  • Yi YS, Ayala-Lopez W, Kularatne SA et al (2009) Folate-targeted hapten immunotherapy of adjuvant-induced arthritis: comparison of Hapten potencies. Mol Pharm 6:1228–1236

    Article  PubMed  CAS  Google Scholar 

  • Yoon KH (2009) Proliferation signal inhibitors for the treatment of refractory autoimmune rheumatic diseases: a new therapeutic option. Ann N Y Acad Sci 1173:752–756

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Mosser DM (2008) Macrophage activation by endogenous danger signals. J Pathol 214:161–178

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

The authors would like to acknowledge Elaine Westrick, Torian Stinette, Kristin Hollingsworth, and Vicky Cross for their technical assistance in animal work.

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  1. Endocyte, Inc., 3000 Kent Avenue, Suite A1-100, West Lafayette, IN, 47906, USA

    Yingjuan Lu

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  2. Christopher P. Leamon
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Correspondence to Yingjuan Lu .

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  1. Section of Medicine, Institute of Cancer Research, Cotswold Road 15, Sutton, SM2 5NG, United Kingdom

    Ann L. Jackman

  2. Endocyte Inc., Kent Avenue 3000, West Lafayette, 47906, Indiana, USA

    Christopher P. Leamon

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Lu, Y., Leamon, C.P. (2011). Targeting Activated Macrophages Via a Functional Folate Receptor for Potential Treatment of Autoimmune/Inflammatory Disorders. In: Jackman, A., Leamon, C. (eds) Targeted Drug Strategies for Cancer and Inflammation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8417-3_10

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