Monday, May 24, 2021 7:29:52 PM
There are potential ways to overcome that https://stm.sciencemag.org/content/13/591/eabd8836.short https://www.mdpi.com/2072-6694/12/9/2612/htm
For some types, peak expansion is more important than long-term persistence https://ascopubs.org/doi/full/10.1200/JCO.20.01467 https://ashpublications.org/bloodadvances/article/4/19/4898/464200/Tumor-burden-inflammation-and-product-attributes
Data from GILD (translational data shows there isn't long-term persistence in many, if not most) https://www.nasdaq.com/press-release/new-four-year-data-show-long-term-survival-in-patients-with-large-b-cell-lymphoma
No, it isn't. GILD's data show that despite optimal product attributes, a 'favourable' TME and robust CAR-T cell expansion, there is incomplete tumour elimination and around 15% of patients relapse with target-negative cancer cells. They are working on ways to overcome that, with an anti-CD19/CD20 CAR-T https://cancerimmunolres.aacrjournals.org/content/4/6/498.long
NTLA is using their own screening platform (CRISPR/Cas9) to identify enhancing edits for CAR-T and TCR-T cell therapies. These look to improve trafficking, infiltration, potency and persistence, while also preventing exhaustion in the TMEs. They have identified both known and potential novel regulators. Importantly, some knockout targets accumulate in multiple, distinct TMEs, while others are TME specific.
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