Immunology and Biotherapies

Highlights

 

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T cells undergo metabolic remodeling to support their function.

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Metabolic pathways impact on T cell differentiation decisions and function in the periphery.

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Manipulating metabolic microenvironments may enhance T cell function in cancer.

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Metabolic pathways could be targeted for the treatment of human disease.

 

In the past several years a wealth of evidence has emerged illustrating how metabolism supports many aspects of T cell biology, as well as how metabolic changes drive T cell differentiation and fate. We outline developing principles in the regulation of T cell metabolism, and discuss how these processes are affected in settings of inflammation and cancer. In this context we discuss how metabolic pathways might be manipulated for the treatment of human disease, including how metabolism may be targeted to prevent T cell dysfunction in inhospitable microenvironments, to generate more effective adoptive cellular immunotherapies in cancer, and to direct T cell differentiation and function towards non-pathogenic phenotypes in settings of autoimmunity.

Via Krishan Maggon

Atara Biotherapeutics, Inc. (Nasdaq:ATRA) today announced that its collaborative partner, Memorial Sloan Kettering Cancer Center (MSK) has received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for Atara's optioned cytotoxic T lymphocytes activated against Epstein-Barr Virus (EBV-CTL) in the treatment of patients with rituximab-refractory, EBV-associated lymphoproliferative disease (EBV-LPD), a type of malignancy occurring after allogeneic hematopoietic cell transplantation (HCT). Allogeneic HCT is also commonly called a bone marrow transplant. - 

 

The T-cell collaboration with MSK consists of three types of CTLs, each focusing on targets involved in cancers and serious infections. Using these cells, the power of the immune system can be employed to attack cancer cells and cells infected with certain viruses. T-cells may be effective even after failure of multiple other agents, and may avoid the toxicities of current treatments in patients with cancers and serious viral infections. CMV-CTLs and EBV-CTLs are currently in Phase 2 clinical trials and WT1-CTLs are currently in Phase 1 clinical studies.

 

The EBV-, CMV- and WT1-targeted T-cell product candidates share a common technology in which third-party donor-derived white blood cells are collected via leukapheresis (white blood cell collection) and are then enriched for T-cells. The T-cells are exposed to certain antigens (proteins that are recognized and attacked by the immune system), and the resulting activated T-cells are characterized and stored for future therapeutic use in a partially human leukocyte antigen, or HLA, matched patient. MSK has developed banks of these off-the-shelf, target-specific T-cell product candidates suitable for investigational use in patients with a wide range of HLA types.

Via Krishan Maggon