Enhanced CD8+ CTL formation for Adoptive Cell Therapies
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A method of generating functionally improved cytotoxic T lymphocytes (CTLs) ex vivo independent of CD4+ T helper cells for use in adoptive cell therapy (ACT). Inhibiting the tyrosine phosphatase PTPN2 achieves enhanced CTL formation and tumour killing.
- Enhanced existing cell therapy platforms - Compatible with the ex vivo reinvigoration of ‘tolerised’ T cells or tumour antigen specific CAR-T cells - 'Proof of Mechanism’ in vivo efficacy - Potential use in single agent and combination therapy applications
Adoptive cell transfer (CARs)
The team has generated data supporting PTPN2 inhibition as an approach to enhancing CTL formation and function. Genetic deficiency of PTPN2 enhances the generation and activation of effector/memory T cells ex vivo (Fig 1.) and enhances the activity of antigen specific CD8+ T cells in the context of adoptive transfer (Fig 2.). Furthermore, pharmacological inhibition of PTPN2 in human CD8+ T cells enhances TCR-mediated proliferation (Fig. 3). Current experiments are aimed at exploring methods of inhibiting PTPN2, using CAR-T cells specific for HER2, both in vitro and in vivo and in combination studies with anti-PD1 or anti-CTLA4 inhibitors.
Licensing
10/06/2015 00:00:00
AU2015274242
JA2016-572566
Others
Monash seeks a partner to develop its technology within an ACT platform. The method has the potential to greatly improve CTL production and consequently, ACT therapy success.
2014-017
澳洲
