Mecanismo Prurido - Ref. PubMed 2011

Update on Pruritus Mechanism

Ikoma A, Cevikbas F, Kempkes C et al. Anatomy and neurophysiology of pruritus. Seminars in Cutaneous Medicine and Surgery 2011; 30: 64-70. Abstract

PubMed ID (PMID): 21767766

Reprint: A. Ikoma 

 

Terapêutica T-Cell Receptor na Atopia Canina - Ensaios

CANINE ATOPIC DERMATITIS and FELINE STOMATITIS

Developing new treatments for large unmet needs

T-Cell Receptor Therapeutics are undergoing the USDA approval process* for canine atopic dermatitis and feline stomatitis. These small peptides are considered therapeutic immune modulators, although they have been shown to work prophylactically as well.  IMULAN is also considering their development for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), and other viral diseases in cats and dogs.

Status of Development: USDA clinical trials

Background: Immune responses are coordinated by the innate immune system via antigen-presenting cells (i.e. monocytes/macrophages) and the acquired immune system by T helper (Th) subsets Th1 and Th2.  Th1 cells promote cellular immunity by the secretion of IL-2, TNF-β, and INF-γ.  Conversely, Th2 cells mainly promote humoral immunity by secreting IL-4, IL-5, IL-10 and IL-13.

It is now well accepted that many diseases are a result of a Th1/Th2 imbalance.  Since Th1 is responsible for cell mediated and antibody mediated (IgG₂) immunity, partial loss of the Th1 component accompanies many chronic infections and makes a host more susceptible to new infections.  This is a tightly balanced system, whereby Th1 cytokines suppress Th2 activity and visa versa.    Therefore, a Th2 bias decreases cell mediated immune surveillance, leaving the host susceptible to pathogens a variety of IgE mediated diseases.  In summary, restoration of normal Th1/Th2 balance is essential for appropriate immune responses and physiological status.
TCR Vaccine Description: The TCR Vaccine is a subcutaneously administered synthetic peptide vaccine that engages the T-cell Receptor (TCR) and has immuno-regulatory and immuno-stimulatory activity.  In lab animal studies, TCR Vaccine has restored cell mediated immunity, normalized Th1/Th2 balance, and reduced viral pathology.  Evidence suggests that TCR Vaccine has long lasting effects after only a few injections.
Key Benefits of the Vaccine:

• Targets a central immunological regulator (T helper cells) for a more comprehensive approach to disease intervention
• Balances numerous cytokines in physiological ratios
• Can be used as a prophylactic or therapeutic vaccine
• Requires no adjuvant or antigen to produce effects
• Proposed long lasting effect on immunity (months to years)
• Synthetically manufactured which reduces contamination issues

Potential Veterinary Indications:

1. Canine: Atopic dermatitis, autoimmune disorders, canine pyoderma, dry eye, infectious otitis externa
2. Feline: Asthma, enteritis, stomatitis, feline leukemia virus (FeLV), feline immunodeficiency virus (FIV)
3. Equine: Small airway disease, uveitis, equine viral infections
4. Bovine: Johne’s disease, M. bovis, mastitis, BLV
5. Swine: PRRSv
6. Across Animal Species: Neoplasia and infection

Clinical Relevance: TCR treatment is not considered a simple anti-idiotype therapeutic vaccination, but rather a general T-cell immunomodulatory therapeutic.  TCR Vaccines have the effect of normalizing the balance between Th1 and Th2 cytokines, conferring the ability of animals to better reject colonization by opportunistic pathogens, reduce IgE mediated disorders, and restore appropriate immune surveillance.  Treatment with TCR peptides has been found to reduce TNF production and restore immune function needed for optimum host defense.  Thus prevention of imbalanced Th1 and Th2 cytokine production by TCR administration could contribute to the normalization of the entire immune response, thereby retarding development of immune dysfunction due to age, pathogen infection, or other challenges.  In addition, restoration of Th1/Th2 balance is a key approach to a variety of non-infectious veterinary diseases including asthma, heaves, atopy, stomatitis, inflammatory bowel disease, cancer, etc.   
* TCR peptides development is being sponsored by IMULAN BioTherapeutics, LLC through our partner.  TCR peptides are not available for commercial distribution or sale.



http://imulan.com/atopy/