And a potential competitor -
sunolmolecular.com
Sunol is a leader in the development of advanced drug discovery platforms and therapeutic drugs based on its proprietary technologies for single-chain T-Cell Receptors (TCR), single-chain major histocompatibility receptors (MHC) and monoclonal antibodies. An experienced team of managers, scientific staff, board of directors and scientific advisory board allows Sunol to rapidly create value for corporate partners through platform technologies that discover novel protein therapeutic and small molecule drugs. Sunol captures value for its shareholders through development of its own in-house products. Sunol's pipeline of therapeutic candidates are indicated for a broad spectrum of diseases including cardiovascular disease, cancer, autoimmune disease such as multiple sclerosis and rheumatoid arthritis, and infectious diseases caused by bacteria and viruses. Sunol has established a dominant proprietary position from the use of single-chain TCR and MHC as therapeutics and diagnostics. Sunol is well positioned with its scTCR and scMHC technology to take advantage of many of the applications which have been validated for antibodies, therapeutics, diagnostics, phage display, small molecule discovery and drug discovery, and to explore other antigens or therapies not targeted by antibodies....
Native TCRs are heterodimers consisting of two transmembrane polypeptide chains, designated alpha and beta, convalently linked to each other by disulfide bonds. The extracellular portion of the alpha/beta heterodimer is structurally similar to the antigen-binding fragment of an Ig molecule, which is composed of variable (V) and constant (C) regions of a light chain and the V and C regions of a heavy chain. The V regions of TCR alpha and beta chains contain short stretches of sequence where the variability between different TCRs is concentrated, forming the hypervariable or complementarity-determining regions (CDRs). Three CDRs in the alpha chain are juxtaposed to three similar regions in the beta chain to form the part of the TCR that specifically recognizes peptide-MHC complexes. The beta chain V domain contains a fourth hypervariable region, which does not appear to participate in antigen recognition but is the binding site for microbial products called super-antigens.
The first report of a TCR beta chain crystal structure revealed a strong interaction between the Vbeta domain and an elbow segment at the N-terminal region of the Cbeta domain. Based on this finding, it was hypothesized that the role of the Cbeta-domain was to provide a scaffold to facilitate proper folding of the antigen-recognition region of the Vbeta domain. Using this information, scientists at Sunol developed an innovative approach by designing a three-domain (Valpha-VbetaCbeta) scTCR for expression of the protein. Subsequently, Sunol scientists have confirmed that the three-domain scTCR (Valpha-VbetaCbeta) format and its fusion proteins are produced as soluble and active molecules in both E. coli and in mammalian cells. In light of these findings, Sunol has moved forward with the cloning and production of several other scTCRs using this three-domain design and has achieved high level expression of soluble and functional protein.
Sunol has succeeded in developing large-scale production of functional scTCRs and scTCR fusion molecules in bacterial and mammalian cells. The availability of large amounts of functional scTCR and scTCR fusion protein greatly facilitates the ability to develop and use novel hybrid molecules to activate and guide CTLs, effector cells or anti-tumor (or anti-viral) drugs to the targeted tumor (or viral-infected) cells...
Second Generation Products
Novel anti-Cancer and anti-Viral agents
Sunol has developed a technology to produce commercial levels of soluble, bioactive, single-chain T-cell receptor (TCR) molecules. These TCR molecules can selectively recognize peptide antigens displayed on a cell surface in the context of MHC molecules, allowing for the recognition of epitopes from intracellular proteins. This ability to recognize antigens from inappropriately expressed intracellular proteins makes TCR agents ideally suited to act as drug delivery vehicles for anti-cancer and anti-viral therapeutics.
Various forms of bifunctional molecules based on a HLA-A2 restricted single-chain TCR (scTCR) recognizing the human p53 antigen have been genetically constructed at Sunol. These scTCR-based fusion proteins, containing either cytokines or the Fc domain of human immunoglobulin, have been produced in a mammalian expression system, purified and characterized. Multiple studies using these novel molecules against human breast tumors in a nude mouse model are currently underway.
Autoimmune Diseases (small molecule drugs)
The interaction between a TCR and MHC-peptide complex results in the activation of T-cells. Small molecules that prevent this interaction could be used to selectively suppress T-cell populations responsible for autoimmune diseases. Sunol is uniquely positioned to screen for such agents because it is one of very few companies with the capability to produce both MHC and TCR as soluble or cell-associated molecules. Experiments using reagents available from existing programs have validated screening methods and demonstrated proof of concept. Sunol plans to institute large-scale screening using a panel of disease associated receptors in development. This novel and specific small molecule approach has the potential to revolutionize the treatment of autoimmune diseases and target immunosuppression.... |
