CD Receptor and Targeting Strategies

  • Darsheen J. Kotak
  • Pooja A. Todke
  • Prajakta Dandekar
  • Padma V. DevarajanEmail author
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 39)


The clusters of differentiation (CD) are cell-surface receptors involved in cellular functions like activation, adhesion, and inhibition. These ubiquitous receptors express elevated levels of CD on cells which can serve as key marker in several cancers and infectious diseases. We emphasize on CD receptors involved in cancer, infections, and immune response. In particular, we cover the physiology and pathophysiology of the CD receptor and track the latest developments in targeted delivery of therapeutics and diagnostics mediated via CD receptor.


Clusters of differentiation CD44 Receptor Cancer Infectious diseases Immunology 



Antibody-conjugated drug


Human epithelial adhesion molecule


B-cell receptor


Binding peptide




Cluster of differentiation


Chlorine 6


Chronic lymphocytic leukemia


Chemotherapeutic monoclonal antibodies


Critical micelle concentration


Complement receptor


Chondroitin sulfate


Cutaneous T-cell lymphoma


Cytotoxic T lymphocytes


Decay acceleration factor


Maytansine derivative 4




Fcgamma receptor




Graphene oxide


Envelope glycoprotein




Hyaluronic acid


Human serum albumin


Human hepatocellular carcinoma cell line


Human colorectal carcinoma cell line


Liver hepatocellular carcinoma


Human immunodeficiency virus type 1


N- (2-hydroxypropyl) methacrylamide


Herpes simplex virus truncated thymidine kinase


Interferon gamma




Immunoreceptor tyrosine-based activation motifs


Lymphocyte-specific protein tyrosine kinase


Indinavir-lipid nanoparticles


Monoclonal antibody


M.D. Anderson and MB stands for Metastasis Breast 231


Multidrug resistance


Major histocompatibility complex


Membrane Spanning 4-Domains A1


Mesoporous silica nanoparticles




Neomycin B-arginine conjugate


non-Hodgkin lymphoma




Pancreatic ductal adenocarcinoma


Polyethylene glycol–poly lactic acid-co-glycolic acid


Polyethylene glycol–poly lactic acid-co-glycolic acid


Photo-induced therapy


Peptide-major histocompatibility complex


Peptide nucleic acids


Protein tyrosine kinase




Red fluorescent protein


Renilla luciferase


Significant toxicity immunodeficient


src homology 2


Solid lipid nanoparticle


T-cell receptor


Triple fusion


Tri-functional immunoliposome


T helper


Triple negative xenograft model of breast cancer


Tumor necrosis factor alpha

ZAP 70

Zeta-chain-associated protein kinase


  1. 1.
    Zola H, editor. Medical applications of leukocyte surface molecules—the CD molecules. Molecular medicine. Springer; 2006. New York, USA.Google Scholar
  2. 2.
    Bernard A, Boumsell L, Dausset J, Milstein C, Schlossman SF. Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies. Specification-classification-nomenclature/Typage leucocytaire Antigenes de differenciation leucocytaire humains reveles par lesanticorps monoclonaux: Rapports des etudes com. Springer Science & Business Media; 2013.Google Scholar
  3. 3.
    Erber WN. Human leucocyte differentiation antigens: review of the CD nomenclature. Pathology. 1990;22(2):61–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, et al. CD molecules 2005: human cell differentiation molecules. Blood. 2005;106(9):3123–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Zola H, Swart B, Banham A, Barry S, Beare A, Bensussan A, et al. CD molecules 2006—human cell differentiation molecules. J Immunol Methods. 2007;319(1–2):1–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Prchal J, Levi MM. Williams hematology. New York: The McGraw-Hill Companies; 2010.Google Scholar
  7. 7.
    Chetty R, Gatter K. CD3: structure, function, and role of immunostaining in clinical practice. J Pathol. 1994;173(4):303–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Alarcon B, Berkhout B, Breitmeyer J, Terhorst C. Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma. delta. epsilon core and single T cell receptor alpha or beta chains. J Biol Chem. 1988;263(6):2953–61.PubMedGoogle Scholar
  9. 9.
    Clevers H, Alarcon B, Wileman T, Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6(1):629–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Garcia KC, Adams JJ, Feng D, Ely LK. The molecular basis of TCR germline bias for MHC is surprisingly simple. Nat Immunol. 2009;10(2):143.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Godfrey DI, Rossjohn J, McCluskey J. The fidelity, occasional promiscuity, and versatility of T cell receptor recognition. Immunity. 2008;28(3):304–14.PubMedCrossRefGoogle Scholar
  12. 12.
    Krangel MS. Mechanics of T cell receptor gene rearrangement. Curr Opin Immunol. 2009;21(2):133–9.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Marrack P, Scott-Browne JP, Dai S, Gapin L, Kappler JW. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu Rev Immunol. 2008;26:171–203.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Morris GP, Allen PM. How the TCR balances sensitivity and specificity for the recognition of self and pathogens. Nat Immunol. 2012;13(2):121.PubMedCrossRefGoogle Scholar
  15. 15.
    Van Der Merwe PA, Dushek O. Mechanisms for T cell receptor triggering. Nat Rev Immunol. 2011;11(1):47.PubMedCrossRefGoogle Scholar
  16. 16.
    Littman DR. The structure of the CD4 and CD8 genes. Annu Rev Immunol. 1987;5(1):561–84.PubMedCrossRefGoogle Scholar
  17. 17.
    Ellmeier W, Sawada S, Littman DR. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu Rev Immunol. 1999;17(1):523–54.PubMedCrossRefGoogle Scholar
  18. 18.
    Rudd CE. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990;11:400–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhou L-J, Ord DC, Hughes AL, Tedder TF. Structure and domain organization of the CD19 antigen of human, mouse, and guinea pig B lymphocytes. Conservation of the extensive cytoplasmic domain. J Immunol. 1991;147(4):1424–32.PubMedGoogle Scholar
  20. 20.
    Pitcher LA, Van Oers NS. T-cell receptor signal transmission: who gives an ITAM? Trends Immunol. 2003;24(10):554–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol. 2009;27:591–619.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Cartron G, Watier H, Golay J, Solal-Celigny P. From the bench to the bedside: ways to improve rituximab efficacy. Blood. 2004;104(9):2635–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Louderbough JM, Schroeder JA. Understanding the dual nature of CD44 in breast cancer progression. Mol Cancer Res. 2011;9(12):1573–86.PubMedCrossRefGoogle Scholar
  24. 24.
    Louderbough JM, Brown JA, Nagle RB, Schroeder JA. CD44 promotes epithelial mammary gland development and exhibits altered localization during cancer progression. Genes Cancer. 2011;2(8):771–81.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, et al. Hyaluronan–CD44 interactions as potential targets for cancer therapy. FEBS J. 2011;278(9):1429–43.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Naor D, Sionov RV, Ish-Shalom D. CD44: structure, function and association with the malignant process. Adv Cancer Res. 1997;71:241–319; Elsevier.PubMedCrossRefGoogle Scholar
  27. 27.
    Sneath R, Mangham D. The normal structure and function of CD44 and its role in neoplasia. Mol Pathol. 1998;51(4):191.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Bychkov A, Jung CK. Aberrant expression of CD20 in thyroid cancer and its clinicopathologic significance. Hum Pathol. 2018;71:74–83.PubMedCrossRefGoogle Scholar
  29. 29.
    Khatri I, Ganguly K, Sharma S, Carmicheal J, Kaur S, Batra SK, et al. Systems biology approach to identify novel genomic determinants for pancreatic cancer pathogenesis. Sci Rep. 2019;9(1):123.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Fedorchenko O, Stiefelhagen M, Peer-Zada AA, Barthel R, Mayer P, Eckei L, et al. CD44 regulates the apoptotic response and promotes disease development in chronic lymphocytic leukemia. Blood. 2013;121(20):4126–36.PubMedCrossRefGoogle Scholar
  31. 31.
    Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018;11(1):64.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Katsetos CD, Fincke JE, Legido A, Lischner HW, de Chadarevian J-P, Kaye EM, et al. Angiocentric CD3+ T-cell infiltrates in human immunodeficiency virus type 1-associated central nervous system disease in children. Clin Diagn Lab Immunol. 1999;6(1):105–14.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Vidya Vijayan K, Karthigeyan KP, Tripathi SP, Hanna LE. Pathophysiology of CD4+ T-cell depletion in HIV-1 and HIV-2 infections. Front Immunol. 2017;8:580.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Pahwa S, Read JS, Yin W, Matthews Y, Shearer W, Diaz C, et al. CD4/CD8 ratio for diagnosis of HIV-1 infection in infants: the Women and Infants Transmission Study. Pediatrics. 2008;122(2):331.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Flynn JL, Goldstein MM, Triebold KJ, Koller B, Bloom BR. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci. 1992;89(24):12013–7.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Tascon RE, Stavropoulos E, Lukacs KV, Colston MJ. Protection against Mycobacterium tuberculosis infection by CD8+ T cells requires the production of gamma interferon. Infect Immun. 1998;66(2):830–4.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Stenger S, Modlin RL. T cell mediated immunity to Mycobacterium tuberculosis. Curr Opin Microbiol. 1999;2(1):89–93.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Prezzemolo T, Guggino G, La Manna MP, Di Liberto D, Dieli F, Caccamo N. Functional signatures of human CD4 and CD8 T cell responses to Mycobacterium tuberculosis. Front Immunol. 2014;5:180.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, et al. The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol. 1993;23(2):403–11.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Carpenter PA, Appelbaum FR, Corey L, Deeg HJ, Doney K, Gooley T, et al. A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease. Blood. 2002;99(8):2712–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Bruno CJ, Jacobson JM. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother. 2010;65(9):1839–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Kuritzkes DR, Jacobson J, Powderly WG, Godofsky E, DeJesus E, Haas F, et al. Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1. J Infect Dis. 2004;189(2):286–91.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Rider DA, Havenith CE, de Ridder R, Schuurman J, Favre C, Cooper JC, et al. A human CD4 monoclonal antibody for the treatment of T-cell lymphoma combines inhibition of T-cell signaling by a dual mechanism with potent Fc-dependent effector activity. Cancer Res. 2007;67(20):9945–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Reusch U, Duell J, Ellwanger K, Herbrecht C, Knackmuss SH, Fucek I, et al., editors. A tetravalent bispecific TandAb (CD19/CD3), AFM11, efficiently recruits T cells for the potent lysis of CD19+ tumor cells. MAbs; 2015: Taylor & Francis. Oxfordshire United KingdomGoogle Scholar
  45. 45.
    Breton CS, Nahimana A, Aubry D, Macoin J, Moretti P, Bertschinger M, et al. A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies. J Hematol Oncol. 2014;7(1):33.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Blanc V, Bousseau A, Caron A, Carrez C, Lutz RJ, Lambert JM. SAR3419: an anti-CD19-Maytansinoid immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res. 2011;17(20):6448–58.PubMedCrossRefGoogle Scholar
  47. 47.
    Sun X, Widdison W, Mayo M, Wilhelm S, Leece B, Chari R, et al. Design of antibody− maytansinoid conjugates allows for efficient detoxification via liver metabolism. Bioconjug Chem. 2011;22(4):728–35.PubMedCrossRefGoogle Scholar
  48. 48.
    Kiprijanov SM. Bispecific antibodies and immune therapy targeting. Drug Deliv Oncol. 2012:441–82.Google Scholar
  49. 49.
    Lin TS. Ofatumumab: a novel monoclonal anti-CD20 antibody. Pharmgenomics Pers Med. 2010;3:51.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Mott PJ, Lazarus AH. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis. PLoS One. 2013;8(6):e65805.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Rao G, Wang H, Li B, Huang L, Xue D, Wang X, et al. Reciprocal interactions between tumor-associated macrophages and CD44-positive cancer cells via osteopontin/CD44 promote tumorigenicity in colorectal cancer. Clin Cancer Res. 2013;19(4):785–97.PubMedCrossRefGoogle Scholar
  52. 52.
    Pietras A, Katz AM, Ekström EJ, Wee B, Halliday JJ, Pitter KL, et al. Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth. Cell Stem Cell. 2014;14(3):357–69.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Ferro M, Giuberti G, Zappavigna S, Perdonà S, Facchini G, Sperlongano P, et al. Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin-C in bladder cancer cells with different mechanisms. Oncol Rep. 2012;27(2):409–15.PubMedGoogle Scholar
  54. 54.
    Liu Y-S, Chiu C-C, Chen H-Y, Chen S-H, Wang L-F. Preparation of chondroitin sulfate-g-poly (ε-caprolactone) copolymers as a CD44-targeted vehicle for enhanced intracellular uptake. Mol Pharm. 2014;11(4):1164–75.PubMedCrossRefGoogle Scholar
  55. 55.
    Schmid D, Park CG, Hartl CA, Subedi N, Cartwright AN, Puerto RB, et al. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nat Commun. 2017;8(1):1747.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Chalouni C, Doll S. Fate of antibody-drug conjugates in cancer cells. J Exp Clin Cancer Res. 2018;37(1):20.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Hellmann I, Waldmeier L, Bannwarth-Escher M-C, Maslova K, Wolter FI, Grawunder U, et al. Novel antibody drug conjugates targeting tumor-associated receptor tyrosine kinase ROR2 by functional screening of fully human antibody libraries using Transpo-mAb display on progenitor B cells. Front Immunol. 2018;9:2490.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Kalim M, Chen J, Wang S, Lin C, Ullah S, Liang K, et al. Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates. Drug Des Devel Ther. 2017;11:2265.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Niculescu-Duvaz I, Springer C. Antibody-directed enzyme prodrug therapy (ADEPT): a review. Adv Drug Deliv Rev. 1997;26(2–3):151–72.PubMedCrossRefGoogle Scholar
  60. 60.
    Xu G, McLeod HL. Strategies for enzyme/prodrug cancer therapy. Clin Cancer Res. 2001;7(11):3314–24.Google Scholar
  61. 61.
    Bagshawe KD. Antibody-directed enzyme prodrug therapy. In: Prodrugs: Springer; 2007. p. 525–40. New York, USAGoogle Scholar
  62. 62.
    Hammer O, editor. CD19 as an attractive target for antibody-based therapy. MAbs; 2012: Taylor & Francis. Oxfordshire United KingdomGoogle Scholar
  63. 63.
    Haisma HJ, Sernee MF, Hooijberg E, Brakenhoff RH, vd Meulen-Muileman IH, Pinedo HM, et al. Construction and characterization of a fusion protein of single-chain anti-CD20 antibody and human β-glucuronidase for antibody-directed enzyme prodrug therapy. Blood. 1998;92(1):184–90.PubMedCrossRefGoogle Scholar
  64. 64.
    Št’astný M, Strohalm J, Plocova D, Ulbrich K, Řı́hová B. A possibility to overcome P-glycoprotein (PGP)-mediated multidrug resistance by antibody-targeted drugs conjugated to N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer carrier. Eur J Cancer. 1999;35(3):459–66.PubMedCrossRefGoogle Scholar
  65. 65.
    Ulbrich K, Strohalm J, Šubr V, Plocová D, Duncan R, Říhová B, editors. Polymeric conjugates of drugs and antibodies for site-specific drug delivery. Macromolecular Symposia; 1996: Wiley Online Library. New Jersey,USAGoogle Scholar
  66. 66.
    Cabrera C, Gutiérrez A, Barretina J, Blanco J, Litovchick A, Lapidot A, et al. Anti-HIV activity of a novel aminoglycoside-arginine conjugate. Antivir Res. 2002;53(1):1–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Yeh P, Landais D, Lemaitre M, Maury I, Crenne J-Y, Becquart J, et al. Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate. Proc Natl Acad Sci. 1992;89(5):1904–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Raufi A, Ebrahim AS, Al-Katib A. Targeting CD19 in B-cell lymphoma: emerging role of SAR3419. Cancer Manag Res. 2013;5:225.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Kazane SA, Axup JY, Kim CH, Ciobanu M, Wold ED, Barluenga S, et al. Self-assembled antibody multimers through peptide nucleic acid conjugation. J Am Chem Soc. 2012;135(1):340–6.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Vaidya T, Straubinger RM, Ait-Oudhia S. Development and evaluation of tri-functional immunoliposomes for the treatment of HER2 positive breast cancer. Pharm Res. 2018;35(5):95.PubMedCrossRefGoogle Scholar
  71. 71.
    Ishida T, Iden DL, Allen TM. A combinatorial approach to producing sterically stabilized (stealth) immunoliposomal drugs. FEBS Lett. 1999;460(1):129–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Allen TM, Mumbengegwi DR, Charrois GJ. Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying drug release rates. Clin Cancer Res. 2005;11(9):3567–73.PubMedCrossRefGoogle Scholar
  73. 73.
    Flasher D, Konopka K, Chamow SM, Dazin P, Ashkenazi A, Pretzer E, et al. Liposome targeting to human immunodeficiency virus type 1-infected cells via recombinant soluble CD4 and CD4 immunoadhesin (CD4-IgG). Biochim Biophys Acta Biomembr. 1994;1194(1):185–96.CrossRefGoogle Scholar
  74. 74.
    Lu L, Ding Y, Zhang Y, Ho RJ, Zhao Y, Zhang T, et al. Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII. Int J Nanomedicine. 2018;13:1927.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Eliaz RE, Szoka FC. Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. Cancer Res. 2001;61(6):2592–601.PubMedGoogle Scholar
  76. 76.
    Jiang T, Zhang Z, Zhang Y, Lv H, Zhou J, Li C, et al. Dual-functional liposomes based on pH-responsive cell-penetrating peptide and hyaluronic acid for tumor-targeted anticancer drug delivery. Biomaterials. 2012;33(36):9246–58.PubMedCrossRefGoogle Scholar
  77. 77.
    Alshaer W, Hillaireau H, Vergnaud J, Ismail S, Fattal E. Functionalizing liposomes with anti-CD44 aptamer for selective targeting of cancer cells. Bioconjug Chem. 2014;26(7):1307–13.PubMedCrossRefGoogle Scholar
  78. 78.
    Dinauer N, Balthasar S, Weber C, Kreuter J, Langer K, von Briesen H. Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes. Biomaterials. 2005;26(29):5898–906.PubMedCrossRefGoogle Scholar
  79. 79.
    Bicho A, Peça IN, Roque A, Cardoso MM. Anti-CD8 conjugated nanoparticles to target mammalian cells expressing CD8. Int J Pharm. 2010;399(1–2):80–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Cirstoiu-Hapca A, Bossy-Nobs L, Buchegger F, Gurny R, Delie F. Differential tumor cell targeting of anti-HER2 (Herceptin®) and anti-CD20 (Mabthera®) coupled nanoparticles. Int J Pharm. 2007;331(2):190–6.PubMedCrossRefGoogle Scholar
  81. 81.
    Sargazi A, Shiri F, Keikha S, Majd MH. Hyaluronan magnetic nanoparticle for mitoxantrone delivery toward CD44-positive cancer cells. Colloids Surf B: Biointerfaces. 2018;171:150–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Hosseinzadeh H, Atyabi F, Varnamkhasti BS, Hosseinzadeh R, Ostad SN, Ghahremani MH, et al. SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against metastatic colon cancer cells. Int J Pharm. 2017;526(1–2):339–52.PubMedCrossRefGoogle Scholar
  83. 83.
    Yu M, Jambhrunkar S, Thorn P, Chen J, Gu W, Yu C. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells. Nanoscale. 2013;5(1):178–83.PubMedCrossRefGoogle Scholar
  84. 84.
    Chen Z, Li Z, Lin Y, Yin M, Ren J, Qu X. Bioresponsive hyaluronic acid-capped mesoporous silica nanoparticles for targeted drug delivery. Chem Eur J. 2013;19(5):1778–83.PubMedCrossRefGoogle Scholar
  85. 85.
    Xu C, He W, Lv Y, Qin C, Shen L, Yin L. Self-assembled nanoparticles from hyaluronic acid–paclitaxel prodrugs for direct cytosolic delivery and enhanced antitumor activity. Int J Pharm. 2015;493(1–2):172–81.PubMedCrossRefGoogle Scholar
  86. 86.
    Li J, Huo M, Wang J, Zhou J, Mohammad JM, Zhang Y, et al. Redox-sensitive micelles self-assembled from amphiphilic hyaluronic acid-deoxycholic acid conjugates for targeted intracellular delivery of paclitaxel. Biomaterials. 2012;33(7):2310–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Yang Y, Zhao Y, Lan J, Kang Y, Zhang T, Ding Y, et al. Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery. Int J Nanomedicine. 2018;13:4361.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Wu R-L, Sedlmeier G, Kyjacova L, Schmaus A, Philipp J, Thiele W, et al. Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells. Sci Rep. 2018;8(1):14913.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Chen S, Yang K, Tuguntaev RG, Mozhi A, Zhang J, Wang PC, et al. Targeting tumor microenvironment with PEG-based amphiphilic nanoparticles to overcome chemoresistance. Nanomedicine. 2016;12(2):269–86.PubMedCrossRefGoogle Scholar
  90. 90.
    Yadav AK, Mishra P, Mishra AK, Mishra P, Jain S, Agrawal GP. Development and characterization of hyaluronic acid–anchored PLGA nanoparticulate carriers of doxorubicin. Nanomedicine. 2007;3(4):246–57.PubMedCrossRefGoogle Scholar
  91. 91.
    Shen H, Shi S, Zhang Z, Gong T, Sun X. Coating solid lipid nanoparticles with hyaluronic acid enhances antitumor activity against melanoma stem-like cells. Theranostics. 2015;5(7):755.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Endsley AN, Ho RJ. Enhanced anti-HIV efficacy of Indinavir after inclusion in CD4 targeted lipid nanoparticles. J Acquir Immune Defic Syndr (1999). 2012;61(4):417.CrossRefGoogle Scholar
  93. 93.
    Li F, Park S-J, Ling D, Park W, Han JY, Na K, et al. Hyaluronic acid-conjugated graphene oxide/photosensitizer nanohybrids for cancer targeted photodynamic therapy. J Mater Chem B. 2013;1(12):1678–86.CrossRefGoogle Scholar
  94. 94.
    Nevala WK, Butterfield JT, Sutor SL, Knauer DJ, Markovic SN. Antibody-targeted paclitaxel loaded nanoparticles for the treatment of CD20+ B-cell lymphoma. Sci Rep. 2017;7:45682.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Kim HS, Cho HR, Choi SH, Woo JS, Moon WK. In vivo imaging of tumor transduced with bimodal lentiviral vector encoding human ferritin and green fluorescent protein on a 1.5 T clinical magnetic resonance scanner. Cancer Res. 2010;70(18):7315–24.PubMedCrossRefGoogle Scholar
  96. 96.
    Wang X, Yang L, Chen Z, Shin DM. Application of nanotechnology in cancer therapy and imaging. CA Cancer J Clin. 2008;58(2):97–110.PubMedCrossRefGoogle Scholar
  97. 97.
    Capolla S, Garrovo C, Zorzet S, Lorenzon A, Rampazzo E, Spretz R, et al. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies. Int J Nanomedicine. 2015;10:4099.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer. 2001;1(2):118.PubMedCrossRefGoogle Scholar
  99. 99.
    Hoffmann RM, Coumbe BG, Josephs DH, Mele S, Ilieva KM, Cheung A, et al. Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs). Oncoimmunology. 2018;7(3):e1395127.PubMedCrossRefGoogle Scholar
  100. 100.
    A study of BI-1206 in combination with rituximab in subjects with indolent B-cell non-Hodgkin lymphoma [updated April 1, 2019; cited 2019 June 1]. Available from:
  101. 101.
    Burges A, Wimberger P, Kümper C, Gorbounova V, Sommer H, Schmalfeldt B, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM× anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007;13(13):3899–905.PubMedCrossRefGoogle Scholar
  102. 102.
    Dose-response study of Ibalizumab (monoclonal antibody) plus optimized background regimen in patients with HIV-1 (TMB-202) [updated May 5, 2014; cited 2019 June 1]. Available from:
  103. 103.
    HuMax-CD4 in non-cutaneous T-cell lymphoma [updated July 11, 2018; cited 2019 June 1]. Available from:
  104. 104.
    Rituximab in treating patients with non-Hodgkin’s lymphoma or Hodgkin’s disease [updated July 11, 2018; cited 2019 June 1]. Available from:
  105. 105.
    Porter DL, Hwang W-T, Frey NV, Lacey SF, Shaw PA, Loren AW, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325.PubMedCrossRefGoogle Scholar
  107. 107.
    Gressett SM, Shah SR. Intricacies of bevacizumab-induced toxicities and their management. Ann Pharmacother. 2009;43(3):490–501.PubMedCrossRefGoogle Scholar
  108. 108.
    Coiffier B, Lepage E, Brière J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.CrossRefGoogle Scholar
  109. 109.
    Craik DJ, Fairlie DP, Liras S, Price D. The future of peptide-based drugs. Chem Biol Drug Des. 2013;81(1):136–47.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Darsheen J. Kotak
    • 1
  • Pooja A. Todke
    • 1
  • Prajakta Dandekar
    • 2
  • Padma V. Devarajan
    • 2
    Email author
  1. 1.Department of Pharmaceutical Sciences &TechnologyInstitute of Chemical TechnologyMumbaiIndia
  2. 2.Department of Pharmaceutical SciencesInsitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of MaharashtraMumbaiIndia

Personalised recommendations