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Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications.

07:00 EST 25th November 2019 | BioPortfolio

Summary of "Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications."

Survival rates for sarcoma patients have plateaued in the past few decades and remain especially grim for those with recurrent or metastatic disease. This has prompted investigation into novel immunotherapies for sarcomas, especially after their recent and well-recognized successes in other cancers. One such modality, the Chimeric Antigen Receptor (CAR) T Cell therapy, has shown promising results in treating B-cell lymphoma and acute lymphoblastic leukemia. This novel therapy functions by fusing a specific antibody derived single-chain variable fragment (scFv) with a T-cell which recognizes a specific tumor-associated antigen (TAA). Several sarcoma-associated antigens (SAA) amenable to CAR-T cell treatment have recently emerged with encouraging results. These include human epidermal growth factor receptor 2 (HER2), disialoganglioside (GD2), interleukin 11 Receptor Subunit Alpha (IL-11RA), fibroblast activation protein (FAP), B7-H3, CD44v6, insulin-like growth factor 1 receptor (IGF-1R), and tyrosine kinase orphan-like receptor 1 (ROR1). Given the limitations of current medical therapies, novel treatment strategies are urgently needed. As a sarcoma treatment modality, CAR-T cell therapy is highly promising and continues to draw interest especially as new clinical trials emerge. Here we review recent breakthrough CAR-T cell studies in sarcoma, the targets which define them, and approaches to minimizing host cytotoxicity.

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This article was published in the following journal.

Name: Cancer treatment reviews
ISSN: 1532-1967
Pages: 101934

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Medical and Biotech [MESH] Definitions

Molecule composed of the non-covalent association of the T-cell antigen receptor (RECEPTORS, ANTIGEN, T-CELL) with the CD3 complex (ANTIGENS, CD3). This association is required for the surface expression and function of both components. The molecule consists of up to seven chains: either the alpha/beta or gamma/delta chains of the T-cell receptor, and four or five chains in the CD3 complex.

Components of the B-cell antigen receptor that function in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. They are expressed almost exclusively by B-LYMPHOCYTES and are markers for B-cell NEOPLASMS.

A component of the B-cell antigen receptor that is involved in B-cell antigen receptor heavy chain transport to the PLASMA MEMBRANE. It is expressed almost exclusively in B-LYMPHOCYTES and serves as a useful marker for B-cell NEOPLASMS.

An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.

Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).

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