Using chimeric antigen receptor (CAR) T cell therapy in solid tumours requires effective T cell tumour infiltration and functional persistence. Adusumilli et al. have found that, in an orthotopic model of lung cancer, administering mesothelin-targeted CAR T cells directly to the lung required fewer cells and achieved longer-term remission than doing so intravenously. This therapeutic efficacy was dependent on early activation of CD4+ T cells and CD28-dependent CD4+ T cell-mediated cytotoxicity, and was also effective at eliminating tumours in extrathoracic, disseminated sites.
References
Adusumilli, P. S. et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci. Trans. Med. 6, 261ra151 (2014)
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Villanueva, T. CAR T cell distribution centres. Nat Rev Cancer 14, 767 (2014). https://doi.org/10.1038/nrc3873
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DOI: https://doi.org/10.1038/nrc3873