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New Routes for Allergen Immunotherapy Thomas M. Kündig Dermatology Zurich University Hospital

University Hospital Zürich. New Routes for Allergen Immunotherapy Thomas M. Kündig Dermatology Zurich University Hospital. T cells. B cells. 10. -. 2. Immunological Memory. 10. -. 4. -. 7. 10. Years. Weeks. Months. Immunological Memory. Strong Memory. Weak Memory.

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New Routes for Allergen Immunotherapy Thomas M. Kündig Dermatology Zurich University Hospital

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  1. University Hospital Zürich New Routes for Allergen Immunotherapy Thomas M. Kündig Dermatology Zurich University Hospital

  2. T cells B cells 10 - 2 Immunological Memory 10 - 4 - 7 10 Years Weeks Months Immunological Memory

  3. Strong Memory Weak Memory

  4. Dose +++

  5. Dose Dependence Placebo 10‘000 SQ-U 100‘000 SQ-U Symptoms UK Immunotherapy Study Group JACI 2006

  6. Spreading

  7. into lymph node Subcutaneous

  8. Distribution Allergen Extract (25h) Subcutaneous injection Injektion into lymph node Senti et al. Curr Opin Allergy Clin Immunol 2009

  9. Intralymphatic Immunotherapy

  10. Intralymphatic Immunotherapy 3 Injections Senti et al. PNAS 2008

  11. Intralymphatic Immunotherapy Hyalnder et al. JACI 2013

  12. Malling et al. (EAACI 2012) Hylander et al. (JACI 2013) IgG4 IgE IgG4 IgE 4 wk Senti et al. PNAS 2009 IgG4 IgE 1wk Symptoms worse Symptoms improved

  13. J Exp Med 1996

  14. Is intralymphatic specific immunotherapy with grass pollen allergen ready for clinical use?Malling, H; Blom, L; Poulsen, B; Poulsen, L; Witten, M “Increasing the treatment dose cannot be advised since systemic reactions were seen in app. 10% of the patients” 3% of 174 inj.

  15. Bakterial DNA Viral RNA LPS …. PAMPS….

  16. Allergen + CpG 6 Injections Creticos et al. NEJM 2006

  17. Allergen + MPL Rosewich, Hum Vaccin Immunother 2013

  18. Route ?

  19. Densitiy of Antigen Presenting Cells

  20. Epicutaneous Immunotherapy

  21. Epicutaneous Immunotherapy 12 Patches 6 Patches Improvement (%)

  22. Intradermal Cat-PAD 4 Injections Patel et al. J Allergy Clin Immunol 2013

  23. Low Dose Intradermal Grasspollen 6 Injections Rotiroti et al. J Allergy Clin Immunol 2012

  24. Dose SIT Distribution SIT Adjuvant SIT Route SCIT

  25. Dose SIT Distribution SIT Adjuvant SIT Route SIT

  26. VLPs SMPH chemical linker diameter = 30 nm

  27. QbG10 G10 Transport into lymph node Uptake into pDC Degradation of protein shell Release of CpG Activation of TLR-9

  28. Antibody response +++ ++ - Induction of auto-antibodies +++ - - Antigen Organisation Organization: low absent high T help Independent Type 1 Bachmann et al. Science 1993

  29. Virus Like Allergen: 1 Injection IgG (log10) 1 Injection Kündig JACI 2006

  30. Allergen Fel d 1

  31. IPCIT: Zero Injections IgG in saliva Fel d 1 in saliva

  32. Allergic patients ILIT SLIT IPCIT SCIT EPIT

  33. Rolf Zinkernagel Gabriela Senti Martin Bachmann Lars French Pal Johansen Franziska Zabel Antonia Fettelschoss DeepaMohanan Ying Wäckerle-Men Christine Tivig Fabian Tay Regine Hofmann Barbara Riond AlleCure Corp. CTLImmunoTherapies MannKind Corp. Cytos Biotechnology ImVision Colby Pharmaceuticals

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