Research ArticleImmunotherapy

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

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Science Translational Medicine  05 Nov 2014:
Vol. 6, Issue 261, pp. 261ra151
DOI: 10.1126/scitranslmed.3010162

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An Amazon Model for CAR T Cell Delivery

The success of chimeric antigen receptor (CAR) T cells in treating otherwise untreatable hematological malignancies has been a flag-bearer for cancer immunotherapy. Yet, moving these therapies to solid tumors has been restricted by T cell infiltration and persistence. Now, Adusumilli et al. take a page from online sellers—setting up regional distribution centers to improve delivery. They found that mesothelin-targeted CAR T cells administered directly to the lung outpaced those administered systemically by both efficacy and persistence in an orthotopic model of lung cancer. What’s more, these effects weren’t restricted to lung, as tumors in extrathoracic sites were also eliminated. If these results hold in patients, regional delivery could improve both the efficacy and efficiency of solid tumor immunotherapy.

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