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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.

Whitemarsh RC, Tep WH, Bradshaw M, Lin G, Pier CL, Scherf JM, Johnson EA, and Pellett S

Characterization of Botulinum Neurotoxin A Subtypes 1 through 5 by Investigation of Activities in Mice, in Neuronal Cell Cultures, and In Vitro

Infect Immun 81(10):3894-902

Publication Date: August 5, 2013

Product Type: iCell GABANeurons

Summary:

iCell Neurons, along with other commonly used in vitro and in vivo models, were used to characterize the various subtypes of BoNT/A. The results showed distinct in vitro and in vivo toxicological properties between the mouse bioassay (MBA) and in vitro human cell models, thus questioning the predictivity of the MBA.

Impact:

This study supports the need to consider not only the mode of the testing (in vivo versus in vitro) but also the species of the model when designing potency assays for current and future pharmaceutical BoNT preparations. iCell Neurons area relevant human model to detect BoNT.