Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2013 Aug 8;122(6):853-4.
doi: 10.1182/blood-2013-06-509604.

Genetic engineering of T-cell receptors: TCR takes to titin

Helen E Heslop  1
Affiliations
Comment

Genetic engineering of T-cell receptors: TCR takes to titin

Helen E Heslop. Blood. .

Abstract

In this issue of Blood, Linette et al report a cautionary tale—a lethal off-target toxicity following T-cell receptor (TCR) optimization to enhance affinity against a tumor-associated antigen, MAGE-A3.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: H.E.H.’s center has a collaborative research agreement with Celgene for developing genetically modified T-cell approaches.

Figures

None
A native TCR recognizes a MAGE-A3 peptide expressed by major histocompatibility complex (MHC) molecules on tumor cells. After affinity enhancement by mutations to the α chain, the TCR now recognizes the tumor cell with enhanced affinity but also recognizes another peptide derived from titin expressed by beating cardiomyocytes that is not recognized by the native TCR.
See this image and copyright information in PMC

Comment on

References

    1. Linette GP, Stadtmauer EA, Maus MV, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122(6):863–871. - PMC - PubMed
    1. Jorritsma A, Schotte R, Coccoris M, de Witte MA, Schumacher TN. Prospects and limitations of T cell receptor gene therapy. Curr Gene Ther. 2011;11(4):276–287. - PubMed
    1. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269–281. - PMC - PubMed
    1. Schmitt TM, Aggen DH, Stromnes IM, Dossett ML, Richman SA, Kranz DM, Greenberg PD. Enhanced-affinity murine TCRs for tumor/self-antigens can be safe in gene therapy despite surpassing the threshold for thymic selection [published online ahead of print May 14, 2013]. Blood. doi:10.1182/blood-2013-01-478164. - PMC - PubMed
    1. Cheever MA, Allison JP, Ferris AS, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323–5337. - PMC - PubMed