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Biology – Therapy

Hillerdal V, Nilsson B, Carlsson B et al.

Uppsala University, Uppsala, Sweden.

 Proc Natl Acad Sci U S A 2012;109:15877–81.

Joy Burchell’s review: The reintroduction of patients’ autologous T cells after their manipulation ex vivo is a promising, although relatively expensive, approach for the treatment of cancer. T cells can be engineered ex vivo in a number of ways, including the introduction of chimeric antigen receptors (CARs) or a relevant T cell receptor (TCR). CARs are chimeric molecules that have the signaling domain of the TCR but the recognition domain of a tumor-associated antibody or ligand. This domain has the ability to recognize the tumor cells and thereby activate the internal signaling domain of the TCR, inducing killing. A domain to activate costimulation is also included in these CARs that has the advantage of recognizing intact antigens and, therefore, negates the need for antigen processing and presentation in major histocompatibility complex (MHC) class I by the tumor cells. Another way in which T cells can be engineered ex vivo is to introduce a TCR that specifically recognizes a processed tumor-associated antigen. In this way, a large proportion of the reinfused T cells can recognize a single tumor-associated antigen.

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