TCR-fused Antigen Binding Receptor (TCR-ABR) CAR Construction Services

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

T cell engineering with an antigen-binding antibody fused to extracellular domain of TCR subunits is a promising cell therapy against solid tumors. This kind of therapy has demonstrated encouraging anti-cancer results in pre-clinical trials. As a leading end-to-end CRO, Creative Biolabs provides talented scientists and cutting-edge technologies to help our clients develop TCR-fused Antigen Binding Receptor (TCR-ABR) CAR-engineered T cells.

What is TCR-fused Antigen Binding Receptor (TCR-ABR) CAR?

T cells play an important role in protecting hosts from pathogens and tumors. Their functions are based on the T-cell receptor (TCR)-CD3 complex, in which TCRαβ heterodimer noncovalently combines with the constant CD3 dimers CD3εγ, CD3εδ, and CD3ζζ. The TCRαβ chains and each subunit of the CD3ϵγ and CD3ϵδ heterodimers comprise an extracellular domain, connecting peptide, transmembrane (TM) domain, and a short cytoplasmic tail. Each of the CD3 ϵ, γ, δ, and ζ chains contains immunoreceptor tyrosine-based activation motifs (ITAMs) that can be phosphorylated to initiate the T-cell signaling transduction pathway. Following TCR/pMHC binding, the CD3 molecules transmit activation signals to the T cell.

Fig.1 The natural TCR complex and five TRuC-containing TCR complexes. (Baeuerle, 2019)

Antigen-binding domains fused to TCR subunits have been shown to efficiently initiate an intact TCR complex reaction against tumor surface antigens. These components are also named synthetic T cell receptor fusion constructs (TRuCs). The scFv used to generate CAR-T cells or single domain antibodies can be fused to the extracellular N-termini of TCRα, TCRβ, CD3γ, CD3δ, or CD3ε subunits, resulting in the activation of target-specific TRuC-T cells. TRuC-T cells are as effective as second-generation CAR-T cells at killing tumor cells. In some tumor models, TRuC-T cells exhibit potent anti-tumor activity. In some other models, TRuC-T cells outperform respective CAR-T cells. TRuC-T cells have been shown to use the entire TCR complex's signaling capacity in an HLA-independent manner.

Advantages of the TCR-ABR-CART cells

Advantages of the TCR-ABR-CART cells.

TCR-fused Antigen Binding Receptor (TCR-ABR) CAR Construction Services

Creative Biolabs has built an end-to-end platform to support our customers' TCR-ABR-CART cell development programs from discovery to pre-clinical studies, combining rich experience with a deep knowledge of advanced technologies in the development of cell therapeutics. We provide TCR-fused Antigen Binding Receptor (TCR-ABR) CAR construction and TCR-ABR-CART cell production services. The scFv sequence will be determined according to the specific targets. The fusion subunit of TCR will be determined based on your specific requirements (TCRα, TCRβ, CD3γ, CD3δ, or CD3ε). The TCR-fused Antigen Binding Receptor (TCR-ABR) CAR genes will be introduced into T cells using lentivirus transfection or other approaches.

Creative Biolabs offers high-quality, innovative products and solutions to help you accelerate TCR-ABR-CART cell therapy discovery and development projects. We are committed to understanding and meeting the quality needs and expectations of our customers. Please contact us to learn more.

Reference

Baeuerle, PA. et al Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response. Nat Commun. 2019 May 7;10(1):2087