Following are some diseases that can be potentially treated with our PEPDEX systems. Our focus will be put on the immunological diseases, such as anti-allergy therapies and anti-cancer vacicines.

Neuroscience

● Neurological diseases

Alzheimer disease (Perry and Greig 2004; Li, Duffy et al. 2010)

Multiple sclerosis (Bielekova et al. 2000; Holz et al. 2000; Jurynczyk et al. 2010)

Parkinson’s disease (Szeto 2006)

Epilesy (Brothers and Wahlestedt 2010)

● Psychiatric diseases

Anxiety disorder (Holmes et al. 2003; Leonard et al. 2008; Steckler 2008; Madaan and Wilson 2009)

Depression (Holmes et al. 2003; Leonard et al. 2008; Madaan and Wilson 2009)

Eating disorder (Brothers and Wahlestedt 2010)

Immunology

● Anti-cancer vaccine

Melanoma(Minor 2011; Schwartzentruber, Lawson et al. 2011)

Cervical cancer (Zwaveling, Ferreira Mota et al. 2002)

● Anti-allergy vaccine

Asthma (Campbell, Buckland et al. 2009)

Rheumatoid arthritis (Holgate and Broide 2003)

Allergic rhinitis (Larche and Wraith 2005) (Takagi, Hiroi et al. 2005)

Immunological therapy

Asthma (John D. Campbell, JEM, 2009) (Campbell, Buckland et al. 2009)

There are many mucosal-associated lymphoid systems in the human body, which can react quickly as they usually lie in the host-environmental interfaces. There are many site-specific names for these immune organs; for instance, they are called gut-associated lymphoid tissue system (GALT). In our delivery system, we aim to send and present our peptides through gut-associated lymphoid tissue, since it is one of the biggest and most sophisticated immune systems inside our body, and the system works pretty well in discriminating the pathogens and common normal flora. We try to manipulate this characteristic to design our anti-allergy peptide.

Microfold cells (Wershil and Furuta 2008), abbreviated M cell, are cells found in the follicle-associated epithelium, especially in guts, and deliver foreign antigen to the underlying dendritic cells. The interaction of dendritic cells with the different types of cognate T-cell decides the outcome of immune responses, either adaptive immune responses against certain pathogens or tolerance establishment. The main determinant of the two polarized responses is not yet clear, but the current assumption points to the different types of T-cells activated after antigenic challenges (Iwasaki and Kelsall, 2001). In our project, we planned to deliver anti-allergic peptide by engineered E. coli, which would carries Fel d1, the major cat allergen, as documented(Campbell, Buckland et al. 2009). The anti-allergic peptide requires repetitive challenges, and thus express the Fel d1 through a constitutive, thermal-inducible promoter, Phs (Taylor, Straus et al. 1984). The constitutive presence of the peptide itself would desensitive the reactive immune cells, and establish the local and systemic tolerance, as proved (MacPherson and Liu 1999).

Reference

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Li Y, et al. (2010) GLP-1 receptor stimulation reduces amyloid-β peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J Alzheimers Dis 19(4): 1205–1219.

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