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Allergen Immunotherapy
University Hospital Zürich New Routes for Allergen Immunotherapy Thomas M. Kündig Dermatology Zurich University Hospital
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Immunological Memory 10 Immunological Memory Weeks Months T cells
- 7 Immunological Memory Weeks Months Years 4 2 T cells B cells
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Weak Memory Strong Memory
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Dose +++
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Dose Dependence Placebo 10‘000 SQ-U 100‘000 SQ-U Symptoms
UK Immunotherapy Study Group JACI 2006
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Spreading
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into lymph node Subcutaneous
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Distribution Allergen Extract (25h)
Subcutaneous injection Injektion into lymph node Senti et al. Curr Opin Allergy Clin Immunol 2009
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Intralymphatic Immunotherapy
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Intralymphatic Immunotherapy
3 Injections Senti et al. PNAS 2008
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Intralymphatic Immunotherapy
Hyalnder et al. JACI 2013
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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
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J Exp Med 1996
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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.
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Bakterial DNA Viral RNA LPS …. PAMPS….
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Allergen + CpG 6 Injections Creticos et al. NEJM 2006
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Allergen + MPL Rosewich, Hum Vaccin Immunother 2013
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Route ?
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Densitiy of Antigen Presenting Cells
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Epicutaneous Immunotherapy
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Epicutaneous Immunotherapy
12 Patches 6 Patches Improvement (%)
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Intradermal Cat-PAD 4 Injections
Patel et al. J Allergy Clin Immunol 2013
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Low Dose Intradermal Grasspollen
6 Injections Rotiroti et al. J Allergy Clin Immunol 2012
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Dose SIT Distribution SIT Adjuvant SIT Route SCIT
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Dose SIT Distribution SIT Adjuvant SIT Route SIT
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VLPs SMPH chemical linker diameter = 30 nm
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QbG10 G10 Transport into lymph node Uptake into pDC Degradation of protein shell Release of CpG Activation of TLR-9
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Antigen Organisation Organization: high low absent Antibody response
++ - +++ - Induction of auto-antibodies +++ T help Independent Type 1 Bachmann et al. Science 1993
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Virus Like Allergen: 1 Injection
IgG (log10) 1 Injection Kündig JACI 2006
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Allergen Fel d 1
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IPCIT: Zero Injections
IgG in saliva Fel d 1 in saliva
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Allergic patients ILIT SLIT IPCIT SCIT EPIT
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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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