Bi-specific T-cell engager
Class of artificial monoclonal antibodies From Wikipedia, the free encyclopedia
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 cells' cytotoxic activity, against cancer cells. BiTE is a registered trademark of Micromet AG (fully owned subsidiary of Amgen Inc).[1]
BiTE molecules are fusion proteins consisting of two single-chain variable fragments (scFvs) of different antibodies, or amino acid sequences from four different genes, on a single peptide chain of about 55 kilodaltons. One of the scFvs binds to T cells via the CD3 receptor, and the other to a tumor cell via a tumor specific molecule.[2][3]
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 cytotoxic 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.[2][4]
This action mimics physiological processes observed during T cell attacks against tumor cells.[4]
BiTEs in clinical assessment or with clinical approvals
Summarize
Perspective
Several BiTEs are currently in preclinical and clinical trials to assess their therapeutic efficacy and safety. [5]
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.[6]
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.[7][8]
Talquetamab
Talquetamab, sold under the brand name Talvey, is a humanized monoclonal antibody used for the treatment of multiple myeloma.[9][10] It is a bispecific GPRC5D-directed CD3 T-cell engager.[9] Talquetamab is a bispecific antibody against two targets: human CD3, a T-cell surface antigen, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen with potential antineoplastic activity.[11] Talquetamab binds both targets, drawing the T cells close to the tumor cells, causing a cytotoxic T-lymphocyte response.[11] It is being developed by Janssen Pharmaceuticals.[12]
The most common adverse reactions include cytokine release syndrome, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.[13]
Talquetamab was approved for medical use in both the United States[9][13][14] and the European Union[15] in August 2023. The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[16]Tarlatamab
Tarlatamab, sold under the brand name Imdelltra, is an anti-cancer medication used for the treatment of extensive-stage small cell lung cancer.[17] It is a bispecific T-cell engager that binds delta-like ligand 3 and CD3.[17]
The most common adverse reactions include cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, and constipation, anemia and nausea.[18]
Tarlatamab was approved for medical use in the United States in May 2024.[18][19] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[20]Tebentafusp
After clinical trials, in January 2022, the US FDA approved tebentafusp (a BiTE targeting the gp100 peptide) for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma.[21]
Epcoritamab
Epcoritamab, sold under the brand name Epkinly, is used for the treatment of diffuse large B-cell lymphoma. Epcoritamab is a bispecific CD20-directed CD3 T-cell engager.
Epcoritamab was approved for medical use in the United States in May 2023,[22][23][24][25][26] in the European Union in September 2023, and in Canada in December 2023.
Further research
Utilizing the same technology, melanoma (with MCSP specific BiTEs) and acute myeloid leukemia (with CD33 specific BiTEs) can be targeted.[27] As of 2008[update], research in this area is active.[27]
Another avenue for novel anti-cancer therapies is re-engineering some of the currently used conventional antibodies like trastuzumab (targeting HER2/neu), cetuximab and panitumumab (both targeting the EGF receptor), using the BiTE approach.[28]
As of 2009[update], BiTEs against CD66e and EphA2 are being developed as well.[29]
References
Further reading
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