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Allergen Immunotherapy

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Presentation on theme: "Allergen Immunotherapy"— Presentation transcript:

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

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

3 Weak Memory Strong 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
4 wk Senti et al. PNAS 2009 IgG IgE 1wk Symptoms worse Symptoms improved

13

14 J Exp Med 1996

15 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.

16 Bakterial DNA Viral RNA LPS …. PAMPS….

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

18 Allergen + MPL Rosewich, Hum Vaccin Immunother 2013

19 Route ?

20 Densitiy of Antigen Presenting Cells

21 Epicutaneous Immunotherapy

22 Epicutaneous Immunotherapy
12 Patches 6 Patches Improvement (%)

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

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

25 Dose SIT Distribution SIT Adjuvant SIT Route SCIT

26 Dose SIT Distribution SIT Adjuvant SIT Route SIT

27 VLPs SMPH chemical linker diameter = 30 nm

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

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

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

31

32 Allergen Fel d 1

33 IPCIT: Zero Injections
IgG in saliva Fel d 1 in saliva

34 Allergic patients ILIT SLIT IPCIT SCIT EPIT

35 Rolf Zinkernagel Gabriela Senti Martin Bachmann Lars French
Pal Johansen Franziska Zabel Antonia Fettelschoss Deepa Mohanan 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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