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Engineering T cells with chimeric antigen receptors (CARs) is an effective method for directing T cells to attack tumors, but may cause adverse side effects such as the potentially lethal cytokine release syndrome. Here the authors show that the T cell antigen coupler (TAC), a chimeric receptor that co-opts the endogenous TCR, induces more efficient anti-tumor responses and reduced toxicity when compared with past-generation CARs. TAC-engineered T cells induce robust and antigen-specific cytokine production and cytotoxicity in vitro, and strong anti-tumor activity in a variety of xenograft models including solid and liquid tumors. In a solid tumor model, TAC-T cells outperform CD28-based CAR-T cells with increased anti-tumor efficacy, reduced toxicity, and faster tumor infiltration. Intratumoral TAC-T cells are enriched for Ki-67 CD8 T cells, demonstrating local expansion. These results indicate that TAC-T cells may have a superior therapeutic index relative to CAR-T cells.
This article was published in the following journal.
Name: Nature communications
TGFαL3-SEB chimeric protein is a synthetic protein, which is produced by combining the third loop (L3) of transforming growth factor-α (TGF-α) with staphylococcal enterotoxin type B. To the best of...
Anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a resounding effect on the treatment of chemotherapy-insensitive aggressive B-cell non-Hodgkin lymphoma (B-NHL). There are now...
Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cel...
Chimeric antigen receptor T (CAR-T) cell therapy provides possibility for the treatment of malignancies since clinical trials have shown that CAR-T therapy has a significant anti-tumor effect. Althoug...
Chimeric antigen receptor (CAR) modified T cells targeting CD19 have resulted in unprecedented durable remissions for patients with relapsed and refractory B cell malignancies. Cytokine release syndro...
A pilot study to determine the safety and efficacy of chimeric antigen receptor T cell (autologous T cells transduced with a lentiviral vector expressing chimeric antigen receptor) persona...
Objectives: The purpose of this study is to evaluate the safety and prognosis of New Cluster of Differentiation Antigen 19-chimeric Antigen Receptor T (nCAR19-T) Cells in the treatment of...
An open label, dose escalating/dose regimen finding clinical study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-claudin18.2 chimeric antigen receptor...
This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected allogeneic T-cells in patients with chemotherapy-resistant or r...
The present study evaluates the safety and efficacy of humanized Chimeric antigen receptor T cells (CAR-T) in treating recurrent or refractory B cell malignancy targeting CD19 with a human...
A cell surface protein-tyrosine kinase receptor that is found to be overexpressed in a significant number of adenocarcinomas. It has extensive homology to and can heterodimerize with the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR), the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Activation of the erbB-2 receptor occurs during heterodimer formation with a ligand-bound erbB receptor family members.
A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF Receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) and the erbB-2 receptor (RECEPTOR, ERBB-2). Overexpression of the erbB-3 receptor is associated with tumorigenesis.
An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE.
A member of the tumor necrosis factor receptor superfamily that specifically binds B-CELL ACTIVATING FACTOR. It is found on B-LYMPHOCYTES and plays a role in maturation and survival of B-cells. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A notch receptor that plays an important role in CELL DIFFERENTIATION in a variety of cell types. It is the preferentially expressed notch receptor in mature B-LYMPHOCYTES.
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...