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Cell therapies

Killer_T_cells_surround_a_cancer_cell_ed

Cytotoxic T cells (green and red) attacking a cancer cell (center) . The T cell on bottom left attached to the cancer cell and preparing to secrete toxic granules (red) to kill the cancer cell.

Image credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, National Institutes of Health

Cell therapies represent a revolutionary approach in the field of cancer biology. Cell therapies utilize living immune cells such as T cells, derived from the patient's own body or from donors, that are redirected towards killing the cancer cells. The first cell therapies involved allogeneic bone marrow transplantations where immune cells from a donor were transplanted into patients suffering from different types of blood cancers. The transplanted donor immune cells killed the cancer cells and have improved outcomes of patients. A more recent example of cell therapies are chimeric antigen receptor (CAR) T cells. In CAR T cell therapy, T cells from the patient are genetically modified to express a CAR that specifically bind to an antigen expressed by the cancer cells. CAR binding to the cancer cell antigen leads to activation of the CAR T cell which then kills the cancer cell. 

CAR T cells

A chimeric antigen receptor (CAR) is a synthetic receptor designed to enhance the ability of immune cells, particularly T cells, to recognize and attack cancer cells. CARs are engineered by combining the extracellular antigen-binding domain of an antibody (called single-chain variable fragment (scFv)), with intracellular signaling domains from the T cell receptor (TCR) signaling molecules (such as the CD3zeta and CD28 or 4-1BB domains).

 

 

 

 

 

 

 

 

 

 

 

The result is a genetically modified T cell that can specifically target cancer cells expressing a particular antigen on their surface. Once the CAR T cell encounters a cancer cell with the corresponding antigen, it becomes activated, leading to the destruction of the cancer cell. CAR T cell therapy is considered standard of care for the treatment of B cell lymphomas and myelomas. CAR T cell therapy is under active development for other solid and hematologic cancers. 

 

 

 

Watch CAR T cells kill cancer cells

The scFv on the CAR T cell is designed to detect the presence of a mutated p53 peptide (produced by mutation in the tumor suppressor gene TP53 in cancer cells). Only the cancer cells express the mutated p53 peptide and the mutation is absent in healthy tissue. Live cell imaging shows two CAR T cells (small dark mobile cells on bottom left) 'scan' the cancer cell (large gray cell at bottom left). This is shortly followed by the death (rapid shrinkage) of the cancer cell, and the CAR T cells wander away.

video credit: Sarah DiNapoli, MD, PhD candidate, Johns Hopkins University

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