PTPN2 deletion in T cells promotes anti-tumour immunity and CAR T cell efficacy in solid tumours
Florian Wiede, Kun-Hui Lu, Xin Du, Shuwei Liang, Katharina Hochheiser, Garron Dodd, Pei Goh, Conor Kearney, Deborah Meyran, Paul Beavis, Melissa Henderson, Simone Park, Jason Waithman, Sheng Zhang, Zhong-Yin Zhang, Jane Oliaro, Thomas Gebhardt, Phillip Darcy, Tony Tiganis
WILEY | Published : 2019
ABSTRACT Although adoptive T cell therapy has shown remarkable clinical efficacy in hematological malignancies, its success in combating solid tumours has been limited. Here we report that PTPN2 deletion in T cells enhances cancer immunosurveillance and the efficacy of adoptively transferred tumour-specific T cells. T cell-specific PTPN2 deficiency prevented tumours forming in aged mice heterozygous for the tumour suppressor p53. Adoptive transfer of PTPN2-deficient CD8+ T cells markedly repressed tumour formation in mice bearing mammary tumours. Moreover, PTPN2 deletion in T cells expressing a chimeric antigen receptor (CAR) specific for the oncoprotein HER-2 increased the activation of the..View full abstract
This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (to T.T., P.K.D.), Sylvia & Charles Viertel Charitable Foundation (T.G.), Cancer Council Victoria (F.W.) and the NIH (Z.Y.).