TriCAR Construction Technology

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

Over the past few years, the emergence of CAR-T technology has set off a revolution in immunotherapy. CAR-T technology uses genetic engineering technology to combine receptors that recognize antigens on the surface of tumor cells with costimulatory factors that activate T cell signaling regions to form a fusion protein, and further transfect them into T cells using a carrier system, thereby enabling T cells to be activated and specifically to kill tumor cells. CAR-T technology has shown a significant effect in the treatment of hematological tumors, however, it still needs to overcome many difficulties in the treatment of solid tumors. The main challenges are the difficulty of identifying tumor-specific targets of solid tumors, the MHC limitation of T cells, and the inhibition of T cells by the microenvironment inside solid tumors.

Creative Biolabs has established an innovative CAR-T technology platform, called TriCAR, based on our state-of-class TriTE (Tri-functional T cell Engager) technology. TriCAR Construction Technology platforms produce first-in-class therapeutics to target at intracellular cancer antigens, to redirect T cells, and to improve in-tumor micro-environment. It is shown TriCAR-T stimulates T cells proliferation and blocks inhibitory pathways by modulating the microenvironment in the solid tumor.

Fig.1 TriTE construct.

TriTE Technology

TriTE, is a fusion protein with unique functions including T cell engagement, T cell stimulation, and checkpoint blocking. TriTE consists of the following components:

R1: antigen binding domain, replaceable with our arsenal of single domain MAR constructs, or with other binding constructs
R2: anti-CD3 for T cell engaging and stimulating
R3 & R4: Sushi domain and IL15 binding pair, wherein IL15 serves as a T cell stimulator
R5: PD1 for binding to PD-L1 on the cancer cell to block the T cell inhibitory pathway.

TriCAR Construction Technology Platform

Fig.2 TriCAR construct.

Creative Biolabs's TriCAR-T technology platform utilizes a part of the proprietary TriTE construct as a multi-functional binding domain. In general, the TriCAR contains an anti-antigen scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T/SILK to simultaneously targeting the antigen-specific cancer cells, blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus making it a tri-functional CAR (Tri-CAR). The modulator domains, IL15 and PD1, significantly improve the in-tumor micro-environment for solid tumor immunotherapies.

Notes:

Creative Biolabs provides a comprehensive list of TriCAR products. Please browse the Product to find the target you are interested in. Or you can contact us to customize TriCAR products tailored to your needs.
The cancer antigen binding domain (R1) can be replaceable. You can use our proprietary TCR-like antibodies targeting MHC antigen complexes, or using any other antibodies or TCRs.

Advantages

Advantage over CAR-T	TriCAR-T binds to both MHC antigen complexes and cell surface targets - more potent for solid tumor immunotherapy.
Advantage over TCR-T	TriCAR-T shows better MHC antigen complex binding specificity and affinity.
TriTE Improves micro-environment for cancer immunotherapy	PD1 blocks the PD-L1/PD1 pathway. IL15 stimulates T cells or NK cells. anti-CD3 engages and stimulates T cells.
More targets	TriMARs bind to intracellular antigens as presented in the MHC antigen complexes. TriCARs carry conventional antibodies that bind to cell surface antigens.
Easy to produce	Binding to both Protein L and Protein A. Easier to generate and produce.

For more detailed information, please feel free to contact us or directly sent us an inquiry.