Bi-specific T-cell engager (BiTE) is a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

activity, against cancer cells. ''BiTE'' is a registered

trademark A trademark (also written trade mark or trade-mark) is a form of intellectual property that consists of a word, phrase, symbol, design, or a combination that identifies a Good (economics and accounting), product or Service (economics), service f ...

of Micromet AG (fully owned subsidiary of Amgen Inc). BiTE molecules are

fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...

s consisting of two

single-chain variable fragment A single-chain variable fragment (scFv) is not actually a fragment of an antibody, but instead is a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins, connected with a short linker peptide of t ...

s (scFvs) of different antibodies, or

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

s from four different genes, on a single

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

chain of about 55

kilodalton The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

s. One of the scFvs binds to T cells via the CD3 receptor, and the other to a tumor cell via a tumor specific molecule.

Mechanism of action

Like other bispecific antibodies, and unlike ordinary monoclonal antibodies, BiTEs form a link between T cells and tumor cells. This causes T cells to exert

activity on tumor cells by producing proteins like perforin and granzymes, independently of the presence of MHC I or co-stimulatory molecules. These proteins enter tumor cells and initiate the cell's

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. This action mimics physiological processes observed during T cell attacks against tumor cells.

BiTEs in clinical assessment or with clinical approvals

Several BiTEs are currently in preclinical and clinical trials to assess their therapeutic efficacy and safety.

Blinatumomab

Blinatumomab links T cells with CD19 receptors found on the surface of B cells. The Food and Drug Administration (US) and the European Medicines Agency approved this therapy for adults with Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia.

Glofitamab

It is a bispecific CD20-directed CD3 T-cell engager. It was approved for medical use in Canada in March 2023, in the United States in June 2023, and in the European Union in July 2023.

Mosunetuzumab

Bispecifically binds CD20 and CD3 to engage T-cells. Mosunetuzumab was approved for medical use in the European Union in June 2022.

Solitomab

Solitomab links T cells with the EpCAM antigen which is expressed by colon, gastric, prostate, ovarian, lung, and pancreatic cancers.

Talquetamab

Tarlatamab

Tebentafusp

After clinical trials, in January 2022, the

US FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

approved tebentafusp (a BiTE targeting the gp100 peptide) for HLA-A*02:01-positive adult patients with unresectable or metastatic

uveal melanoma Uveal melanoma is a type of eye cancer in the uvea of the eye. It is traditionally classed as originating in the iris, choroid, and ciliary body, but can also be divided into class I (low metastatic risk) and class II (high metastatic risk). S ...

Epcoritamab

Epcoritamab, sold under the brand name Epkinly, is used for the treatment of

diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 ...

. Epcoritamab is a bispecific CD20-directed CD3 T-cell engager. Epcoritamab was approved for medical use in the United States in May 2023, in the European Union in September 2023, and in Canada in December 2023.

Further research

Utilizing the same technology,

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

(with MCSP specific BiTEs) and

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympt ...

(with CD33 specific BiTEs) can be targeted. , research in this area is active. Another avenue for novel anti-cancer therapies is re-engineering some of the currently used conventional antibodies like

trastuzumab Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together ...

(targeting

HER2/neu Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The ...

cetuximab Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal a ...

and panitumumab (both targeting the

EGF receptor The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. The epidermal growth factor recept ...

), using the BiTE approach. , BiTEs against

CD66e Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) also known as CD66e (Cluster of Differentiation 66e), is a member of the carcinoembryonic antigen (CEA) gene family. Functions In the literature, CEACAM5 is often used as a syn ...

and EphA2 are being developed as well.