Targeted Cancer Therapies

Radiation therapy technologies

We are developing disruptive radiation therapy technologies towards improved therapeutic ratios.

Our focus areas are:

• Boron neutron capture therapy (BNCT): In work led by Kate Ricketts, we are developing solutions towards optimised BNCT, an emerging oncology modality which focuses radiation damage targeted on the cellular scale.
• TARGeted Intraoperative radioTherapy (TARGIT-IORT): Jayant Vaidya and colleagues developed and implement one-shot radiation given during surgery to treat over 45,000 breast cancer patients in 38 countries worldwide.
• FLASH proton therapy: An ultra-high dose rate burst of radiation to the target shown to reduce healthy tissue toxicity without compromising anti-cancer effect.

Gene and Cell Therapies

We are harnessing molecular genetics and synthetic biology to develop the next generation of gene and cell therapies. This is led by John Counsell.

Our ongoing projects include:

• Engineering immunotherapies: In collaboration with GOSH we are developing novel chimeric antigen receptor (CAR) technologies and tumour-targeted vectors that can activate immune cells in vivo, as a therapy for solid tumours.
• Engineering Viral Vector Technologies: We engineer gene delivery technologies  including HIV-1 based lentiviral and adeno-associated virus (AAV) vectors. We assist companies and academic collaborators to develop and refine their own vector IP.
• Gene therapy: We develop genetic interventions for inherited metabolic diseases and muscular dystrophy. Our gene therapy technologies include µDystrophin engineering, gene editing and full-length dystrophin gene transfer.

Nanomedicine

We implement the engineerability and targetability of nanomedicine towards improved cancer targeting and healthy tissue sparing, led by Kate Ricketts. Our research themes include:

• Nanoparticle-enhanced radiotherapy.
• In vitro models of nanoparticle transport and microdistribution.
• Nanomedicine imaging pipelines.

Our facilities

Established by John Counsell, the UCL BioFoundry is a state-of-the-art facility to support the design and synthesis of DNA, mRNA, and viral vector technologies for research applications. We have 2 'BioXp' DNA benchtop synthesisers with capability to generate up to 1,000 individual DNA constructs weekly. We generate viral vectors (lentivirus and AAV) as a service.

Centre of Targeted Cancer Therapies

We have biomedical, physics, engineering and clinical expertise, and leading gene vector technologies and imaging pipelines.

Alumni

• Dr Alvena Kureshi
• Dr Rawiya Al Hosni
• Dr Judith Pape
• Dr Philip Barrett
• Dr Auxtine Micalet

Select publications

1. Vaidya JS, Bulsara M, Baum M, Wenz F, et al. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial. BMJ. 2020 Aug 19;370: m2836.
2. Zhang Z, Counsell JR. Non-canonical capsid engineering highlights new possibilities for AAV vectorology. Mol Ther Methods Clin Dev. 2024 Mar 6;32(1): 101221.
3. Ahmad R, Schettino G, Royle G ... Ricketts K. Radiobiological Implications of Nanoparticles Following Radiation Treatment. Part Part Syst Charact. 2020 Apr;37(4): 1900411.
4. Vaidya JS, Bulsara M, Baum M, Wenz F, et al. New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer. Br J Cancer. 2021 Aug;125(3): 380-389.
5. Asgarian Z, Siam A, Counsell JR. One transgene, two myopathies: an MTM1 'cross gene therapy' for BIN1 deficiency? Brain. 2023 Oct 3;146(10): 3966-3968.
6. Vaidya JS, Vaidya UJ, Baum M, Bulsara MK, Joseph D, Tobias JS. Global adoption of single-shot targeted intraoperative radiotherapy (TARGIT-IORT) for breast cancer-better for patients, better for healthcare systems. Front Oncol. 2022 Aug 11;12: 786515.
7. Ricketts K, Ahmad R, Beaton L, Cousins B, et al. Recommendations for clinical translation of nanoparticle-enhanced radiotherapy. Br J Radiol. 2018 Dec;91(1092): 20180325.
8. Vaidya JS, Bulsara M, Saunders C, Flyger H, et al. Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival: Long-term Results From the TARGIT-A Randomized Clinical Trial in Early Breast Cancer. JAMA Oncol. 2020 Jul 1;6(7): e200249. Erratum in: JAMA Oncol. 2020 Jul 1;6(7): 1123.
9. Pini V, Mariot V, Dumonceaux J, Counsell J, O'Neill HC, Farmer S, Conti F, Muntoni F. Transiently expressed CRISPR/Cas9 induces wild-type dystrophin in vitro in DMD patient myoblasts carrying duplications. Sci Rep. 2022 Mar 8;12(1): 3756.
10. Alzahrani H, Richards S, Sedgwick I, Seller P, Konstantinidis A, Royle G, Ricketts K. Image quality determination of a novel digital detector for X-ray imaging and cone-beam computed tomography applications. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol 968. 2020 Jul. 163914.