Antibody Inducing Polyvalent Cancer Vaccines

Vaccines may be monovalent (also called univalent) or multivalent (also called polyvalent). A polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. Polyvalent vaccines will probably be required due to tumor cell heterogeneity, heterogeneity of the human immune response and the correlation between overall antibody titer against tumor cells and antibody effector mechanisms. Creative Biolabs is a world leader in the field of cancer vaccine development. With our extensive experience and advanced platform, we are therefore confident in offering the best development services for polyvalent cancer vaccines. We guarantee the finest results for our customers all over the world.

Cancer Cell-Surface Targets for Vaccine Construction

• Gangliosides GM2, GD2, GD3 and Fucosyl GM1

Gangliosides are sialic acid containing glycolipids that are expressed at the cell surface with their lipid (ceramide) moiety incorporated into the cell surface lipid bilayer. Most gangliosides considered as potential targets for cancer therapy are expressed primarily in tissues and tumors of neuroectodermal origin. This is true for the melanoma, sarcoma and neuroblastoma antigens GM2, GD2 and GD3, and the small cell lung cancer antigen, fucosyl GM1. Surprisingly, however, GM2 has also recently been identified in a number of epithelial cancers and at the luminal surfaces of a variety of normal epithelial tissues.

• Neutral Glycolipids Lewis^y and Globo H

Lewis^y (Le^y) and Globo H antigens are found at the cell surface of epithelial cancers primarily expressed as glycolipids attached to the lipid bilayer through their ceramide, but they are also O-linked via -OH groups of serine or threonine to mucins and N-linked via the NH2 group of asparagine in other proteins. Whether expressed as glycolipids or glycoproteins, the immune response against these antigens is predominantly against the carbohydrate moiety. The expression of Le^y and Globo H on various types of cancer cells has been well documented. They are expressed in lesser amounts on a variety of normal tissues, again at the lumen border of ducts and in secretions as described for TF and sTn. Monoclonal antibodies against each have shown good localization to human cancers in vivo.

• TF, Tn and sTn Antigens

Mucins are major cell surface antigens in breast cancers and a variety of other epithelial cancers. They are primarily large extracellular molecules made up of multiple copies of serine and threonine rich tandem repeats. Though mucins (including carbohydrate and peptide epitopes) are also expressed on some normal tissues they have proved to be excellent targets for anti-cancer attack for two reasons: 1) Expression on normal tissues is largely restricted to the ductal border of secretory cells, a site largely inaccessible to the immune system. Cancer cells, on the other hand, have no patent ducts and so accumulatemucins. 2) Peptide backbones of cancer mucins are not fully glycosylated and glycosylation that does occur is not complete. Glycosylation of cancer mucins with mono- or di-saccharides such as Thomsen- Friedenreich antigen (TF), Tn and sialylated Tn (sTn) O-linked to serines or threonines is especially common. Expression of these mono- and disaccharides correlates with a more aggressive phenotype and a more ominous prognosis. Both active and passive immunotherapy trials have identified TF, Tn and sTn antigens as uniquely effective targets for cancer targeting and immunotherapy.

• Polysialic Acid

The “embryonic” form of neural cell adhesion molecule (N-CAM) is expressed on the cell surface of embryonic tissues, occasional neuroendocrine cells and a variety of neuroendocrine tumors including SCLC, neuroblastomas, and carcinoids. Embryonic N-CAM undergoes a series of post-translational modifications, with the acquisition of polysialic acid chains. Several monoclonal antibodies, including mAb 735 and NP-4, recognize these long polysialic acid chains and have allowed characterization of this potential antigen in both normal and malignant tissue.

• Mucin MUC1

The peptide backbones of tumor mucins may also be targets for immune attack. Mucin 1 (MUC1) is a major mucin in breast cancers and is also expressed in a variety of other epithelial cancers. It contains a large extracellular component made up of multiple copies of a 20-amino acid tandem repeat, and a cytoplasmic tail. Though mucins (including carbohydrate and peptide epitopes) are also expressed on some normal tissues they have proved to be excellent targets for anticancer attack for the same reasons noted for sTn, TF, and Tn.

• KSA

Human adenocarcinoma associated antigen (KSA), also called epithelial glycoprotein (EGP) and EpCAM, is a 40 kDa glycoprotein associated with the cell surface of most adenocarcinomas and with the corresponding normal tissues (once again at secretory borders).

• PSMA

Prostate specific membrane antigen (PSMA) is a 100 kDa integral, type II membrane protein with acidic dipeptides activity which is highly expressed in primary and metastatic prostate cancer, and to a lesser extent in normal prostate tissue. PSMA expression increases with disease progression. Recently PSMA has also been detected in tumor vascular endothelium from a variety of cancers as well as at much lower levels in some normal tissues, including duodenal mucosa and some proximal renal tubules. The relevance of PSMA as a target is emphasized by successful targeting of prostate cancer with ProstaScint, an ¹¹¹In-labelled anti-PSMA mAb that has been licensed by FDA for this purpose.

• CA125

CA125 is a mullerian duct differentiation antigen expressed in some normal secretory tissues but overexpressed in ovarian cancer and some other cancers. It has been used as a serum marker for monitoring patients with ovarian cancer since it was first identified in 1981 using a murine monoclonal antibody. It has recently been identified as a mucin (MUC16) with high seronine, threonine and proline content and many (probably >60) partially conserved tandem repeats (156aa each) at the N-terminal region. The C-terminus contains a possible transmembrane region and a potential tyrosine phosphorylation site.

Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.