Combining acoustic cavitation and immunotherapy for the treatment of paediatric cancers

Project ID: 2228cd1309 (You will need this ID for your application)

UCL Lead department: Mechanical Engineering

Project Summary:

Immunotherapy has significantly extended cancer patient survival for previously incurable diseases. One form of immunotherapy, CAR T cell therapy, has shown efficacy against haematological malignancies, but is less effective in soft tissue tumours, in part due to low uptake. In this multi-institutional collaborative project, we have obtained pilot data, using a paediatric neuroblastoma model which suggest that acoustic cavitation (microbubble induced mechanical damage in the target – termed histotripsy) can enhance the anticancer effects of CAR T cells. We hypothesize that the main mode of action is through vascular disruption and/or inflammatory signalling to increase the concentration of CAR T cells within the tumour microenvironment. This project aims to derive a better understanding of the mechanisms involved in order to optimise treatment conditions, and thus to improve clinical options for paediatric neuroblastoma. The PhD researcher will be working with 3 groups (Ultrasonics Group at UCL Mechanical Engineering under Prof. Saffari; Developmental Biology at UCL Great Ormond Street Institute of Child Health under Prof. Anderson and Division of Radiotherapy and Imaging at The Institute of Cancer Research under Prof. ter Haar) to study how acoustic cavitation enhances CAR T cell immunotherapy and inducing a stronger immunological anti-cancer response in a range of neuroblastoma models. Areas of interest include: comparison of different histotripsy tissue liquefaction protocols and identification of the optimum timing between CAR T cell injection and ultrasound exposure. The primary goal of this study is to investigate the mechanisms by which histotripsy (acoustic cavitation) potentially transforms immunologically ‘cold’ tumours into responsive ‘hot’ tumours. The student will be trained in therapeutic ultrasound experimental techniques and acoustic cavitation physics, and by working alongside cell biologists and oncologists they will acquire a unique set of laboratory skills which would place them at the forefront of bioengineering research.