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.

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

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

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

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

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

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

RT @_amandachen: Excited to share that my PhD work is out in @Nature today! We engineered armoured CAR T cells to express therapeutic paylo….

I am incredibly thankful for the opportunity to work on such an exciting project, alongside a collaborative and supportive team, in an inspiring research environment with exceptional mentorship.

This work would not have been possible without the combined efforts of everyone in the Beavis and Darcy labs, as well as our collaborators.

Ultimately, we found that NR4A2 was highly tumour-restricted, which made it ideal for delivering potent cytokines like IL-12. On the other hand, RGS16 exhibited strong intratumoural activity and was optimal for mediating the anti-tumour effects of less potent cytokines like IL-2.

Truly fortunate to work alongside Amanda, the best co-first author I could ever ask for. Incredibly motivated, dedicated and genuinely inspiring. Together, we tested various target gene/payload combinations.

After the screen in my first year, Paul recognised how complementary Amanda’s and my work were, and that’s when we combined our efforts to push this project forward.

I was lucky that Amanda had already developed the CRISPR KI protocol before I joined, allowing me to dive straight into screening different genes in CAR T cells. This led to the identification of NR4A2 and RGS16 as optimal KI sites to support tumour-specific transgene expression.

Taking a gap year due to COVID-19 border closures and starting a PhD without lab experience was challenging. But with the unwavering support of my supervisors and lab members, I was able to learn everything from scratch — their patience and guidance truly made all the difference.

I am incredibly grateful to my supervisors for giving me the chance to do a PhD with them at @PeterMacRes and to work on such an exciting project.

I was first drawn to this project by its description in the PhD advertisement, so I applied despite having zero wet lab experience. Never even held a pipette gun, but driven by pure curiosity in cancer immunology & synthetic biology!.

The science part? Already covered by @paulbeavis4 and @_amandachen. Now, here’s the story of how I got to join this incredible team and work on the project.