Amanda Chen

Excited to share that my PhD work is out in @Nature today! We engineered armoured CAR T cells to express therapeutic payloads only at the tumour site, to improve their safety and efficacy for the treatment of solid cancers. 1/14 nature.com/articles/s4158…

@ImmunoPodcast @paulbeavis4 @Nature Thank you for the thorough summary of our paper!

🛡️ Drs. @_AmandaChen, Kah Min Yap, Imran House, Phillip Darcy, and @PaulBeavis4 developed #CRISPR-edited armored CAR T cells that deliver cytokines directly to tumor sites. @Nature article: go.nature.com/3I8Nk8S Discussion: bit.ly/3Gu9UIF

Nature research paper: Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery go.nature.com/4le7GMB

Wow amazing work using NR4A2/RGS16 promoters to trigger IL‑12/IL‑2 only in tumors is brilliant! A big game‑changer in CAR‑T therapy. Huge congrats to @_amandachen and colleagues ! 🎉

Therefore, gene editing strategies that enable precise control of transgene expression will be key to designing more effective CAR T cells. Congratulations @kevin_sek, and thank you to everyone who contributed to this work! 5/5

This study highlights a novel application of our tumour-inducible expression system: extending the therapeutic lifespan of an armoured CAR T cell by restricting its enhanced effector functions to the tumour site. 4/5

Proud to have been part of this study led by @kevin_sek, @paulbeavis4 & Phil Darcy in @NatureComms now! We showed that tumour-specific expression of A1R in CAR T cells protects against adenosine-mediated exhaustion, and enhances anti-tumour efficacy. 1/5 nature.com/articles/s4146…

Pleased to present the latest work from the lab published in @NatureComms in work led by @kevin_sek: nature.com/articles/s4146…

@SrimayeeV @Nature Thanks Sri!

@_amandachen @Nature Congrats Amanda!! 🥳

Excited to share that my PhD work is out in @Nature today! We engineered armoured CAR T cells to express therapeutic payloads only at the tumour site, to improve their safety and efficacy for the treatment of solid cancers. 1/14 nature.com/articles/s4158…

Wow. Endogenous regulatory circuit-generated armoured CAR T cells. Seriously cool. Basic premise is to “armour” CAR T cells by getting them to express pro-inflammatory cytokines only when in tumours. Since T cells in tumours get exhausted and up-regulate PD1, the first approach was to knock in TNFα under the PD1 promoter. So when tumours try to switch off T cells… they actually switch them on! Such a cool concept. They tested other pro-inflammatory cytokines under PD-1 promoter-driven expression, and found most worked, except IL-12 under this promoter caused severe toxicity, because PD-1 expression outside the tumour seems to be too high. So then they screened for genes up-regulated in tumours versus spleen and picked out some top candidates whose knockout didn’t affect T cell function. They honed in on expressing IL-12 knocked into the NR4A2 locus, and expressing IL-2 knocked into the RGS16 locus. These worked unbelievably well. The team also developed a one-step knock-in protocol for knocking in both the CAR to the TRAC locus and the cytokine to the NR4A2/RGS16 locus. This is so awesome. Hopeful for the clinical trials in the future!

@AdamRochussen @Nature Thank you! Very happy to share our protocol with you. I'll message you directly!

@_amandachen @Nature Amazing science. I’d be really keen to try the knockin AAV6 strategy. Is there a protocol you might be able to share with me? I saw 50% efficiency in the paper and was kinda blown away!

Happy to share a new study led by all-star team @_amandachen, @kahmin98, @ImranHouse, Phil Darcy and @paulbeavis4 showing that tumor site-specific delivery of potent cytokines is a safe way to boost CAR T cell treatment against solid cancers! nature.com/articles/s4158…

@EvanWeberPhD @Nature Thanks Evan!

@_amandachen @Nature Congrats Amanda, amazing work!

@GamerPhilDoc @Nature Thank you, Philipp!

@_amandachen @Nature Elegant work! Your tumor-site-specific payload delivery in CAR-T cells redefines precision for solid cancer therapies. A brilliant solution to systemic toxicity challenges.

CAR T cells are engineered to drive tumor-restricted expression of proinflammatory cytokines by repurposing endogenous gene regulatory mechanisms nature.com/articles/s4158… #NBThighlight

In the news today: Peter Mac scientists have developed “Precision Guided Munition” CAR T-cells – smart immune cells that target solid tumours directly. In lab models, they wiped out breast, colon & ovarian tumours with cure rates near 100%! More: petermac.org/about-us/news-…

Dedicating my first post on X to share some exciting news — our work is out today in @Nature! 🎉 Co-first authored with the amazing lab buddy @_amandachen, and guided by our incredible supervisors @paulbeavis4, Phil & @ImranHouse. nature.com/articles/s4158…

Fresh off the press! ♨️ Scientists, including @_amandachen & @paulbeavis4, developed a #CRISPR knock-in strategy that leverages the regulatory mechanisms of endogenous genes to drive transgene expression in a tumor-localized manner. @nature | go.nature.com/3I8Nk8S