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.

RT @ImmunoPodcast: 🛡️ Drs. @_AmandaChen, Kah Min Yap, Imran House, Phillip Darcy, and @PaulBeavis4 developed #CRISPR-edited armored CAR T c….

RT @Nature: Nature research paper: Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery.

RT @Michelkahi: 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….

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.

This was overcome by restricting A1R to the tumour site using the endogenous NR4A2 promoter (as per our engineering strategy published yesterday: , leading to robust therapeutic responses. 3/5.

While CAR T cells with constitutive A1R expression exhibited significantly improved effector functions in vitro, they lacked efficacy in vivo due to accelerated T cell exhaustion and reduced persistence. 2/5.

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.

RT @paulbeavis4: Pleased to present the latest work from the lab published in @NatureComms in work led by @kevin_sek:. .

RT @AdamRochussen: Wow. Endogenous regulatory circuit-generated armoured CAR T cells. Seriously cool. Basic premise is to “armour” CAR T….

RT @JunyunLai: Happy to share a new study led by all-star team @_amandachen, @kahmin98, @ImranHouse, Phil Darcy and @paulbeavis4 showing th….

RT @NatureBiotech: CAR T cells are engineered to drive tumor-restricted expression of proinflammatory cytokines by repurposing endogenous g….

RT @PeterMacCC: In the news today: Peter Mac scientists have developed “Precision Guided Munition” CAR T-cells – smart immune cells that ta….

RT @kahmin98: Dedicating my first post on X to share some exciting news — our work is out today in @Nature! 🎉 Co-first authored with the am….

RT @celltherapynews: Fresh off the press! ♨️ . Scientists, including @_amandachen & @paulbeavis4, developed a #CRISPR knock-in strategy tha….

RT @LabWaggoner: NR4A2 & RGS16 promoters support delivery of cytokines (e.g. IL-12) directly to the tumor site, leading to enhanced antitum….

RT @paulbeavis4: Delighted to share our new approach to enhance CAR T cell function in solid tumours published today @Nature. In this work….

Lastly, thank you to everyone in the Beavis and Darcy labs for all the help with our crazy, huge experiments. This work was truly a team effort, and I feel so lucky to have done a PhD in such a collaborative lab. 14/14.

And a special thank you to @v_wiebking_md (previously in the Porteus lab), who helped us establish our CRISPR/Cas9 + AAV6 protocol and got me through the first roadblock in my PhD! 13/14.

@paulbeavis4, @ImranHouse and Phil Darcy, thank you for your unwavering support over the years and for making me the scientist and person that I am today. I am so grateful for the amazing PhD experience that you have given me. 12/14.