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Human CD22 : Scientific background and Collaboration Opportunity

Scientific background
CD22 is a cell surface molecule belonging to the SIGLEC family of lectins. Its extracellular domain binds cis alpha2,6-linked sialic acid ligands.

CD22 has many functions in the regulation of B cells. Some of them are regulated by the ligand binding while others are ligand independent as outlined bellow:

A. CD22 is a regulatory coreceptor of the B cell receptor (BCR). It has a significant role in ascertaining signaling thresholds for B cell activation. This is dependent on the proximity of the CD22 to the BCR, which is governed by the sialic acid binding. There is still no complete model for how this ligand binding controls CD22 function, since sialic acid binding is capable of both promoting and inhibiting CD22 and B cell functions. CD22 contains motifs that are structurally identical to known activation and inhibition motifs. Of these, it contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs).1

B. CD22 is responsible for regulation of peripheral B cell balance and survival.2

C. CD22 promotes the BCR induced cell cycle progression and development of immature B cells.3

D. CD22 has a role in the regulatory loop controlling the CD19/CD21-Src-family protein tyrosine kinase (PTK). CD22 is responsible for intensifying the Src-family kinase activation. Furthermore, CD22 and CD19, both regulators of BCR signaling, have their own regulatory network. CD19 regulates CD22 phosphorylation while CD22 inhibits CD19 phosphorylation.4

E. CD22 is a regulator of CD40 signaling.5

F. CD22 expressed on dendritic cells regulate the maintenance of long lived mature B cells in the bone marrow.6

Moreover, CD22-deficient mice have a shorter life span and a reduced number of mature B cells in the bone marrow and in circulation.

Therapeutic Potential
Due to CD22 extensive role regulating B cells, there are many autoimmune diseases that have either CD22+ or CD22- deficiencies. Here are two examples.

CD22+:
Hairy Cell Leukemia (HCL)
Hairy cell Leukemia is a mature B cell neoplasm. The name is from the micro-filament projections that make the cells appear “hairy” under a microscope. These projections strongly express CD22. These cells build up in the bone marrow and interfere with the production of normal levels of white and red blood cells. HCL also infiltrate the spleen. Recent studies on CD22 have also shown that patients with hairy cell leukemia have higher levels of sCD22 proportional to the concentration of circulating hairy cell leukemia cells.7

CD22-:
Rheumatoid Arthritis (RA)
B cells in patients with RA are hyperactivated. In these patients, CD22+ B cells significantly decrease in comparison to the control group, while CD5+ CD22- B cells significantly increased in RA patients.8

Anti-CD22
There has been many clinical investigation with anti-CD22 (including Epratuzumab - humanized antibody ; Amgen) over the last few years for many diseases, include: non-Hodgkin’s lymphomas (NHL), autoimmune diabetes, B cell lymphoma, hairy cell leukemia, follicular lymphoma, rheumatoid arthritis, vasculitis, systemic lupus erythematosus (SLE), Sjogren’s syndrome, acute lymphoblastic leukemia (ALL) and others.

Anti-CD22 has not reached the therapeutic market yet. The reason for the many clinical investigations is the high level of cellular internalization of anti-CD22 by CD22 as compared to other antigens. This makes anti-CD22 ideal for delivery of radioisotopes or immunotoxins to malignant cells.9

Collaboration Opportunity
SBH Sciences Recombinant human CD22 is a soluble 75.0 kDa (666 amino acid residues) protein which corresponds to the extracellular domain of CD22. The protein is produce by CHO cells and it is glycosylated.

SBH Sciences is looking for partners to investigate SBH Sciences soluble CD22 as therapeutic agent as well as diagnostic tool (e.g., to follow patients with HCL).

We are open for suggestions and would be pleased to hear from you.

References:
1. Walker JA et al, Immunology, 123(6) 314-25, Mar 2008
2. Tedder TF et al, Advances in Immunology, 88 1-50, 2005
3. Santos L et al, Journal of Immunology, 180(7) 4561-9, Apr 2008
4. Fujimoto M et al, Journal of Dermatological Science, 46(1) 1-9, Apr 2007
5. Tedder TF et al, Advances in Immunology, 88 1-50, 2005
6. Santos L et al, Journa of Immunology, 180(7) 4561-9, Apr 2008
7. Matsushita K et al, Blood, 112(6) 2272-7, Sep 2008
8. Nakiri Y et al, Clinical Rheumatology, 26(10) 1721-3, Oct 2007
9. Du X et al, Cancer Research, 68(15) 6300-5, Aug 2008





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