Skip to main content
SpringerLink
Log in
Book cover

Biomaterials in Regenerative Medicine and the Immune System pp 257–277Cite as

Artificial Antigen-Presenting Cells: Biomimetic Strategies for Directing the Immune Response

  • Chapter
  • First Online:

Abstract

Antigen-specific immune modulation and bioengineered immunotherapy have many applications in medicine. One promising technology to achieve the goal of immune control is the use of artificial antigen-presenting cells (aAPCs). aAPCs are synthetic constructs that mimic natural APCs in their ability to direct and maintain a T cell response. Several design criteria are important in the construction of an aAPC including its biomaterial composition, the size and shape of the aAPC for T cell interaction, the type and density of surface proteins presented, the delivery of soluble signals, and the recreation of the dynamic immunological synapse. Various aAPCs have been developed as therapeutics including those that activate the immune system against cancer or infectious disease and others that suppress the immune system in the context of autoimmunity. Additional research into the design and application of aAPCs could unlock the full potential of this technology to direct the immune response.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Delsing CE, Gresnigt MS, Leentjens J, et al. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infect Dis. 2014;14(1):166.

    Article  Google Scholar 

  2. Lodhi S, Lamb K, Meier- Kriesche H. Solid organ allograft survival improvement in the United States: the long- term does not mirror the dramatic short- term success. Am J Transpl. 2011;11(6):1226–35.

    Article  Google Scholar 

  3. Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 2011;17(11):3520–6.

    Article  Google Scholar 

  4. Oelke M, Krueger C, Giuntoli RL 2nd, Schneck JP. Artificial antigen-presenting cells: artificial solutions for real diseases. Trends Mol Med. 2005;11(9):412–20.

    Article  Google Scholar 

  5. Knight SC, Stagg AJ. Antigen-presenting cell types. Curr Opin Immunol. 1993;5(3):374–82.

    Article  Google Scholar 

  6. Rossi M, Young JW. Human dendritic cells: potent antigen-presenting cells at the crossroads of innate and adaptive immunity. J Immunol. 2005;175(3):1373–81.

    Article  Google Scholar 

  7. Ohteki T, Koyasu S. Role of antigen-presenting cells in innate immune system. Arch Immunol Ther Exp—Engl Ed. 2001;49:S47–52.

    Google Scholar 

  8. Adalid-Peralta L, Fragoso G, Fleury A, Sciutto E. Mechanisms underlying the induction of regulatory T cells and its relevance in the adaptive immune response in parasitic infections. Int J Biol Sci. 2011;7(9):1412.

    Article  Google Scholar 

  9. Gascoigne NRJ, Zal T. Molecular interactions at the T cell–antigen-presenting cell interface. Curr Opin Immunol. 2004;16(1):114–9.

    Article  Google Scholar 

  10. Capece D, Verzella D, Fischietti M, Zazzeroni F, Alesse E. Targeting costimulatory molecules to improve antitumor immunity. BioMed Res Int. 2012;2012:926321.

    Google Scholar 

  11. Von Bubnoff D, De La Salle H, Wessendorf J, Koch S, Hanau D, Bieber T. Antigen- presenting cells and tolerance induction. Allergy. 2002;57(1):2–8.

    Google Scholar 

  12. Kaliński P, Hilkens CM, Wierenga EA, Kapsenberg ML. T-cell priming by type-1and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today. 1999;20(12):561–7.

    Article  Google Scholar 

  13. Kalinski P. Dendritic cells in immunotherapy of established cancer: roles of signals 1, 2, 3 and 4. Curr Opin Investig Drugs. 2009;10(6):526.

    Google Scholar 

  14. Alarcon B, Mestre D, Martinez-Martin N. The immunological synapse: a cause or consequence of T-cell receptor triggering? Immunology. 2011;133(4):420–5.

    Article  Google Scholar 

  15. Valitutti S, Coombs D, Dupre L. The space and time frames of T cell activation at the immunological synapse. FEBS Lett. 2010;584(24):4851–7.

    Article  Google Scholar 

  16. Mescher M. Surface contact requirements for activation of cytotoxic T lymphocytes. J Immunol. 1992;149(7):2402–5.

    Google Scholar 

  17. Steenblock ER, Fahmy TM. A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells. Mol Ther. 2008;16(4):765–72.

    Article  Google Scholar 

  18. Fifis T, Gamvrellis A, Crimeen-Irwin B, et al. Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol. 2004;173(5):3148–54.

    Article  Google Scholar 

  19. Sunshine JC, Perica K, Schneck JP, Green JJ. Particle shape dependence of CD8+ T cell activation by artificial antigen presenting cells. Biomaterials. 2014;35(1):269–77.

    Article  Google Scholar 

  20. Chacon JA, Wu RC, Sukhumalchandra P, et al. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy. PloS One. 2013;8(4):e60031.

    Article  Google Scholar 

  21. Rudolf D, Silberzahn T, Walter S, et al. Potent costimulation of human CD8 T cells by anti-4-1BB and anti-CD28 on synthetic artificial antigen presenting cells. Cancer Immunol, Immunother. 2008;57(2):175–83.

    Article  Google Scholar 

  22. Matic J, Deeg J, Scheffold A, Goldstein I, Spatz JP. Fine tuning and efficient T cell activation with stimulatory aCD3 nanoarrays. Nano Lett. 2013;13(11):5090–7.

    Article  Google Scholar 

  23. Ansen S, Butler MO, Berezovskaya A, et al. Dissociation of its opposing immunologic effects is critical for the optimization of antitumor CD8+ T-cell responses induced by interleukin 21. Clin Cancer Res. 2008;14(19):6125–36.

    Article  Google Scholar 

  24. Steenblock ER, Fadel T, Labowsky M, Pober JS, Fahmy TM. An artificial antigen-presenting cell with paracrine delivery of IL-2 impacts the magnitude and direction of the T cell response. J Biol Chem. 2011;286(40):34883–92.

    Article  Google Scholar 

  25. Prakken B, Wauben M, Genini D, et al. Artificial antigen-presenting cells as a tool to exploit the immunesynapse’. Nat Med. 2000;6(12):1406–10.

    Article  Google Scholar 

  26. Mossman KD, Campi G, Groves JT, Dustin ML. Altered TCR signaling from geometrically repatterned immunological synapses. Science. 2005;310(5751):1191–3.

    Article  Google Scholar 

  27. Mandal B, Bhattacharjee H, Mittal N, et al. Core–shell-type lipid–polymer hybrid nanoparticles as a drug delivery platform. Nanomed: Nanotechnol, Biol Med. 2013;9(4):474–91.

    Google Scholar 

  28. Butler MO, Hirano N. Human cell- based artificial antigen- presenting cells for cancer immunotherapy. Immunol Rev. 2014;257(1):191–209.

    Article  Google Scholar 

  29. Butler MO, Ansen S, Tanaka M, et al. A panel of human cell-based artificial APC enables the expansion of long-lived antigen-specific CD4+ T cells restricted by prevalent HLA-DR alleles. Int Immunol. 2010;22(11):863–73.

    Article  Google Scholar 

  30. Maus MV, Thomas AK, Leonard DG, et al. Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB. Nat Biotechnol. 2002;20(2):143–8.

    Article  Google Scholar 

  31. Torikai H, Reik A, Liu PQ, et al. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood. 2012;119(24):5697–705.

    Article  Google Scholar 

  32. Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005;106(1):376–83.

    Article  Google Scholar 

  33. Sun S, Cai Z, Langlade-Demoyen P, et al. Dual function of Drosophila cells as APCs for naive CD8+ T cells: implications for tumor immunotherapy. Immunity. 1996;4(6):555–64.

    Article  Google Scholar 

  34. Latouche J-B, Sadelain M. Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells. Nat Biotechnol. 2000;18(4):405–9.

    Article  Google Scholar 

  35. Steenblock ER, Wrzesinski SH, Flavell RA, Fahmy TM. Antigen presentation on artificial acellular substrates: modular systems for flexible, adaptable immunotherapy. Expert Opin Biol Ther. 2009;9(4):451–64.

    Article  Google Scholar 

  36. Turtle CJ, Riddell SR. Artificial antigen-presenting cells for use in adoptive immunotherapy. Cancer J. 2010;16(4):374–81.

    Article  Google Scholar 

  37. Tham EL, Jensen PL, Mescher MF. Activation of antigen-specific T cells by artificial cell constructs having immobilized multimeric peptide—class I complexes and recombinant B7–Fc proteins. J Immunol Methods. 2001;249(1):111–9.

    Article  Google Scholar 

  38. Shalaby WS, Yeh H, Woo E, et al. Absorbable microparticulate cation exchanger for immunotherapeutic delivery. J Biomed Mater Res Part B: Appl Biomater. 2004;69(2):173–82.

    Article  Google Scholar 

  39. Engelhard VH, Strominger JL, Mescher M, Burakoff S. Induction of secondary cytotoxic T lymphocytes by purified HLA-A and HLA-B antigens reconstituted into phospholipid vesicles. Proc Natl Acad Sci U S A. 1978;75(11):5688–91.

    Article  Google Scholar 

  40. Zappasodi R, Di Nicola M, Carlo-Stella C, et al. The effect of artificial antigen-presenting cells with preclustered anti-CD28/-CD3/-LFA-1 monoclonal antibodies on the induction of ex vivo expansion of functional human antitumor T cells. Haematologica. 2008;93(10):1523–34.

    Article  Google Scholar 

  41. Oelke M, Maus MV, Didiano D, June CH, Mackensen A, Schneck JP. Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nat Med. 2003;9(5):619–24.

    Article  Google Scholar 

  42. Perica K, Tu A, Richter A, Bieler JG, Edidin M, Schneck JP. Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumor activity. ACS Nano. 2014;8(3):2252–60.

    Article  Google Scholar 

  43. Fadel TR, Steenblock ER, Stern E, et al. Enhanced cellular activation with single walled carbon nanotube bundles presenting antibody stimuli. Nano Lett. 2008;8(7):2070–6.

    Article  Google Scholar 

  44. Perica K, De Leon Medero A, Durai M, et al. Nanoscale artificial antigen presenting cells for T cell immunotherapy. Nanomed: Nanotechnol Biol Med. 2014;10(1):119–29.

    Article  Google Scholar 

  45. Lu X, Jiang X, Liu R, Zhao H, Liang Z. Adoptive transfer of pTRP2-specific CTLs expanding by bead-based artificial antigen-presenting cells mediates anti-melanoma response. Cancer Lett. 2008;271(1):129–39.

    Article  Google Scholar 

  46. Butler MO, Lee J-S, Ansén S, et al. Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Clin Cancer Res. 2007;13(6):1857–67.

    Article  Google Scholar 

  47. Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995;333(16):1038–44.

    Article  Google Scholar 

  48. Papanicolaou GA, Latouche JB, Tan C, et al. Rapid expansion of cytomegalovirus-specific cytotoxic T lymphocytes by artificial antigen-presenting cells expressing a single HLA allele. Blood. 2003;102(7):2498–505.

    Article  Google Scholar 

  49. Lu X-L, Liang Z-H, Zhang C-E, Lu S-J, Weng X-F, Wu X-W. Induction of the Epstein-Barr Virus latent membrane protein 2 antigen-specific cytotoxic T lymphocytes using human leukocyte antigen tetramer-based artificial antigen-presenting cells. Acta Biochim Biophys Sin. 2006;38(3):157–63.

    Article  Google Scholar 

  50. Brodie SJ, Lewinsohn DA, Patterson BK, et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat Med. 1999;5(1):34–41.

    Article  Google Scholar 

  51. Schütz C, Oelke M, Schneck JP, Mackensen A, Fleck M. Killer artificial antigen-presenting cells: the synthetic embodiment of a ‘guided missile’. Immunotherapy. 2010;2(4):539–50.

    Article  Google Scholar 

  52. Schütz C, Fleck M, Mackensen A, et al. Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells. Blood. 2008;111(7):3546–52.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Biomedical Engineering, Materials Science and Engineering, Ophthalmology, and Neurosurgery, Translational Tissue Engineering Center, and Institute for Nanobiotechnology, Johns Hopkins School of Medicine, Baltimore, USA

    Dr. Jordan J. Green

  2. Department of Biomedical Engineering, Translational Tissue Engineering Center, and Institute for Nanobiotechnology, Johns Hopkins School of Medicine, 400 N Broadway, Smith 5017, 21231, Baltimore, MD, USA

    Randall A. Meyer

Authors
  1. Randall A. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dr. Jordan J. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jordan J. Green .

Editor information

Editors and Affiliations

  1. Albert Einstein College of Medicine, Bronx, New York, USA

    Laura Santambrogio

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Meyer, R., Green, J. (2015). Artificial Antigen-Presenting Cells: Biomimetic Strategies for Directing the Immune Response. In: Santambrogio, L. (eds) Biomaterials in Regenerative Medicine and the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-18045-8_14

Download citation

Publish with us

Policies and ethics

Search

Navigation