Common Antibody Targets

Anti-cancer monoclonal antibodies are very selective for cancer cells; they are able to identify which cells are malignant by markers on the cell surface. CD stands for cluster of differentiation.  Each unique surface molecule or group of molecules that characterize a malignant cell is given a CD number assigned by an international group of scientists. (Some refer to CD as classification determinant.)  Over 300 numbers have been assigned and additional ones may be put on the list in the future. CD molecules can be receptors or ligands that activate receptors and they often play a role in adhesion (keeping malignant cells together) or signal transduction.  Monoclonal antibodies used for therapy target the molecules and the MAb attaches to the cancer cell.  When biochemists discover a candidate surface molecule, it gets a CD number once two specific monoclonal antibodies are shown to bind to the molecule.  If scientists can find only one MAb that will bind, the molecule gets a “w” in its designation.  For instance: CDw999.

GD2 is a disialoganglioside (a glycolipid) present on surface of some cancer cells

HER2 – human epidermal growth factor receptor 2

Nectin-4 – one of four transmembrane glycoproteins (nectin-1 to -4).  (Some recent research has referred to a fifth, Nectin-5, but it is not clear this has been accepted by the biochemistry community.)  The nectins are considered cellular adhesion molecules.  Nectin-4 is known to contribute to tumor proliferation but scientists do not know how it does so.

Somatostatin receptor – found expressed at relatively higher levels in many tumor cells

TROP-2 – Trophoblast cell surface antigen 2 or tumor-associated calcium signal transducer 2.  A glycoprotein involved in cell signaling pathways associated with tumorigenesis.  TROP-2 has been linked to increased tumor growth; it is overexpressed in most human solid epithelial cancers.

BCMA – B-cell maturation antigen, also called CD269.

CCR4 – C-C chemokine receptor type 4 – CD194

CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152, protein receptor

EGFR – Epidermal growth factor receptor, a tyrosine kinase receptor

PD-L1 – programmed death ligand 1 – aka CD274.  The PD-1 (programmed cell death-1) receptor is expressed on the surface of activated T cells. Its ligands, PD-L1 and PD-L2, are expressed on the surface of dendritic cells or macrophages. PD-1 and PD-L1/PD-L2 belong to the family of immune checkpoint proteins that act as co-inhibitory factors that can halt or limit the development of the T cell response.  An analysis of new cancer drugs approved from 2009 to 2020 found that 35 percent acted on the PD-1 target.

SLAMF7 aka CD319 – signaling lymphocyte activation molecule family member 7

VEGF – Vascular endothelial growth factor – protein in biochemical pathway that promotes the growth of new blood vessels.

VEGF explained

Vascular endothelial growth factor encompasses a number of biochemicals that play a part in the body’s functioning, especially in the development of new blood vessels.  VEGF is also called vascular permeability factor or VPF.  Subtypes include endocrine gland-derived vascular endothelial growth factor (EG-VEGF), VEGF-A (the first type discovered), VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F (snake venom VEGF), and placenta growth factor (PlGF), which is important in the development of organs in embryos.

In the body, VEGF increases the permeability of the blood vessels and makes migration of cells easier.  It also promotes mitosis of the endothelial cells that line the blood vessels and hence causes angiogenesis.  New blood vessels arise from existing blood vessels through “sprouting” or “intussusception”.  Scientists have sought to interfere in this process with drugs that stop angiogenesis as a way to slow or stop the growth of cancerous tumors.

The other part of the VEGF mechanism is the cell receptors that VEGF binds to.  These are called VEGF receptors, or VEGFRs.  VEGFR-1 and VEGFR-2 are prevalent in blood vessels cells – the cells that line the blood vessels.  VEGFR-3 is prevalent in cells that line the structures that lymph travels through.

GD2 explained

Sphingolipids are a type of biomolecule that play roles in cell recognition and signaling.  They often sit on the surface of cells.  There are many types of sphingolipids and they do many things in single-celled organisms as well as mammals.  One type, the gangliosides, are important in human immunology as they function as cell markers.  The GD2 type of disialoganglioside shows up much more often on cancerous cells than on non-malignant ones, and drug designers seek to exploit this fact by creating antibodies that target GD2.

GD2 shows up in neuroblastomas, melanomas, retinoblastomas, and Ewing sarcomas

The medicines dinutuximab and naxitamab are on the market for neuroblastoma treatment as well as moxetumomab pasudotox for leukemia.  These and other investigational compounds either directly kill the malignant cells (apoptosis), make the malignant cells visible to the body’s immune cells which destroy the cancerous cells through phagocytosis, or disrupt the cellular membrane, leading to loss of integrity and inability to multiply.

It is also thought that these drugs can stop malignant cells in the blood or lymph from adhering to the extracellular body structures or taking up residence in the bone marrow.

EGFR explained

Epidermal growth factor (EGF) is a biochemical or group of biochemicals (proteins) instrumental in tissue development.  The factor stimulates division of cells and differentiation of cells.

EGF is part of a binary system – it connects to the epidermal growth factor receptor (EGFR) on the surface of cells.  The EGFR is also a protein that goes across the cell membrane and hence plays a part in the body’s signaling.  EGFR is part of the ErbB family of receptors.  It is also called ErbB-1 and HER1.

In many cancers, the EGFR is active.  Biochemists describe the situation by saying EGFR is overexpressed, dysregulated or mutated.  Medicines intended to block EGFR activity have been developed and include Gefitinib, Lapatinib, and Neratinib.

Related receptors in the ErbB family are HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4).  These can also play a part in cancer progression and are potential targets for medicines.

Trop-2 Explained

In healthy cells, this protein spans the cell membrane and plays a role in tissue growth. It has stem cell like properties.  It can also play a part in several cancer pathways.  Trop-2 is overexpressed in breast, lung, colorectal, pancreatic, and ovarian carcinomas, among others.   Trop2 is also known as tumor-associated calcium signal transducer 2. trophoblast antigen 2, cell surface glycoprotein Trop-2/Trop2, and gastrointestinal tumor-associated antigen GA7331.  The gene that encodes it is TACST.