NanoTag´s own programs have resulted in the development and characterization of several single-domain antibodies specific to targets with therapeutic and diagnostic potential.
NanoTag is looking for B2B opportunities to bring these or new single-domain antibodies to the next level. Please contact us if you have interest in partnering with us.
Human CD19 is a 95 KDa glycoprotein belonging to the superfamily of immunoglobulins (UniProt Link). CD19 is expressed in all B lineage cells and is classified as a type I transmembrane protein, with a cytoplasmic C-terminus and extracellular N-terminus. The main proposed roles of CD19 are to recruit multimolecular complexes at the surface of mature B cells (e.g., with CD21 and CD81) and lower the signaling pathways threshold for BCRs. CD19 is a major biomarker for B lymphocyte development, and various lymphoma diagnoses and is being used as a target for different leukemia immunotherapies.
Originally called leukocyte common antigen (LCA), human CD45 is a type I transmembrane protein that belongs to the protein tyrosine phosphatase family (UniProt Link). CD45 is present on the surface of most differentiated hematopoietic cells, with the exception of erythrocytes and plasma cells. CD45 plays an essential role in the regulation of T- and B-cell antigen receptor signaling. Its extracellular functions through direct interaction with components of the antigen receptor complexes (considered as a co-stimulator) or by activating various intracellular kinases involved in the antigen receptor signaling using its phosphatase activity located in two intracellular domains. Antibodies against CD45 are used in flow cytometry and immunohistochemistry to differentiate between immune cell types, as well as to differentiate between histological sections from lymphomas and carcinomas.
CD56, also known as a Neural Cell Adhesion Molecule (NCAM; UniProt Link), is a type I transmembrane glycoprotein discovered originally on the surface of neurons, glia, and skeletal muscle. Evidence suggests that it plays a role in the cell-matrix and cell-cell adhesion, neurite outgrowth, synaptic plasticity, and learning. However, CD56 has also been found in some lines of the hematopoietic system, becoming a prototypic marker of Natural killer (NK) cells. Antibodies against NCAM are being tested as immunotherapies. In particular, to attack neuroblastomas of young patients and as radio-immuno-localization of metastases. Different antibody-based therapies using CD56 as a target are continuously being evaluated on other cancer types.
CD127 is a ~80 kDa type I transmembrane glycoprotein, also known as IL-7 receptor subunit alpha (IL-7Rα; UniProt Link). CD127 is found on normal B cell precursors but not on mature B lymphocytes. It is also expressed by thymocytes, most peripheral T lymphocytes, a subset of monocytes, and a subset of CD34+ cells. The binding of IL-7 with its receptor is important for the stimulation of mature and immature T cells and immature B cell proliferation and development. Functional defects in this protein may be associated with the pathogenesis of severe combined immunodeficiency (SCID); however, several diseases are associated with CD127, such as T-cell acute lymphoblastic leukemia, multiple sclerosis, and rheumatoid arthritis.
Tumor necrosis factor-alpha (TNFa) is primarily produced as a 233-amino acid-long type II transmembrane protein (UniProt Link) which needs to form stable homotrimers to have a biological function. Macrophages mainly produce TNFa, but various other cell types can produce it. TNFa can also become soluble (cytokine activity) with the help of the metalloprotease TNF alpha converting enzyme (TACE or ADAM17). However, the soluble trimeric TNFa (~50kDa) tends to dissociate if concentration drops below the nanomolar range, thereby losing its bioactivity. TNFa is involved in a plethora of processes, and arguably, its most prominent role is associated with different inflammatory responses and autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, and refractory asthma.
Immunoglobulin isotype M (IgM) is first expressed as a monomer on the surface of immature B cells as part of the B cell receptor (BCR). IgM+ B cells secrete pentameric IgM antibodies formed by five Ig monomers connected via disulfide bonds upon antigenic stimulation. The pentameric IgM also contains a polypeptide J-chain, which links two of the monomers and facilitates secretion at mucosal surfaces. As IgM antibodies are expressed early in a B cell response, they are rarely highly mutated and have broad antigen reactivity, thus providing an early response to a wide range of antigens without the need for T cell help. IgM antibodies circulating are mainly responsible for the agglutination of red blood cells if the recipient of a blood transfusion receives blood that is not compatible with their blood type.
L-Selectin is a glycosylated type I transmembrane protein that is commonly found on the cell surfaces of T cells. It is a member of cell adhesion and homing receptors, and it plays a relevant role in the calcium-dependent interaction between lymphocytes and endothelial cells. CD62L is considered to act as a homing receptor for lymphocytes allowing the entrance into secondary lymphoid tissues via endothelial capillaries.
HSA is a highly glycosylated globular monomeric protein of ~66 kDa produced and secreted in the liver. HSA is the most abundant protein in human blood plasma, constituting about half of the serum protein. HSA´s main function is believed to be the regulation of the osmotic pressure of blood. However, albumin can also help in the transport of a wide variety of molecules, such as water, hormones, Ca2+, Na+, K+, fatty acids, bilirubin, and possible some drugs. Albumin has been of great interest to the pharmaceutical industry due to its non-toxicity, great abundance in plasma, and, importantly, its ability to maintain drugs in circulation.
CTLA-4 is a protein on T lymphocytes (a type of immune cell) that helps to keep the body’s immune response in check. When CTLA-4 binds to another protein called B7, it stops T lymphocytes from destroying other cells, including cancer cells. Some cancer drugs, called immune system checkpoint inhibitors, are used to block CTLA-4. When this protein is blocked, it releases the “brakes” of the immune system and increases the ability of T cells to destroy cancer cells. We have developed a high affinitity single-domain antibody that is able to efficiently block CTLA-4 from binding to CD80 and CD86.
This project aims to label anti-PDL1 nanobodies developed by NanoTag Biotechnologies GmbH and validate them in vitro using human cell lines. Initially, the Helmholtz Zentrum Dresden Rossendorf (HZDR) company Fluorizon will develop a method to label the nanobodies with radioisotopes without affecting their biological function. The labeled nanobodies will then be tested on human cell lines provided by HZDR, specifically developed for characterizing therapeutic PD-L1 antibodies.
This project is co-financed by funds from the EU (EFRE) and Niedersachen (SER)