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August 2013

Cameron BJ, Gerry AB, Dukes J, Harper JV, Kannan V, Bianchi FC, Grand F, Brewer JE, Gupta M, Plesa G, Bossi G, Vuidepot A, Powlesland AS, Legg A, Adams KJ, Bennett AD, Pumphrey NJ, Williams DD, Binder-Scholl G, Kulikovskaya I, Levine BL, Riley JL, Varela-Rohena A, Stadtmauer EA, Rapoport AP, Linette GP, June CH, Hassan NJ, Kalos M, and Jakobsen BK

Identification of a Titin-derived HLA-A1-presented Peptide as a Cross-reactive Target for Engineered MAGE A3-directed T Cells

Sci Transl Med 5(197):197ra103

Publication Date: August 7, 2013

Product Type: iCell Cardiomyocytes

Summary:

A T cell-based adoptive immunotherapy was developed and deemed to be free of off-target recognition or safety worries by extensive preclinical investigations. Administration to humans resulted in separate severe cardiotoxicity-related adverse event and fatality. Subsequent investigations showed cross-reactivity with cardiac Titin in a highly species-specific manner that was detectable in iCell Cardiomyocytes but not primary cultures of human cardiac cells maintained under the same conditions.

Impact:

This research demonstrates the need for culture systems that more fully recapitulate the native condition, even for highly specific immune-based drug discovery efforts.