With collaborator Sarel Fleishman (Weizmann Institute of Science, Israel), we have developed and validated a panel of de novo designed transmembrane domains (TMDs) that form stable and specific dimeric, trimeric and tetrameric structures in cell membranes. We used these to enforce the corresponding oligomeric states in second-generation chimeric antigen receptors (CARs) against the solid tumour antigen HER2 and showed that both tumour control and cytokine production scaled in direct proportion to the designed oligomeric structure of the TMD (see eLife 2022).

Ongoing work in this program is focused on (1) expanding our panel of available TMD sequences and structures, (2) testing the clinical relevance of these new tools for optimising the safety/efficacy profiles of cellular immunotherapies in specific cancer contexts and (3) developing even more sophisticated applications for these sequences in the CAR T-cell space.

Project resources: 

• 'Goldilocks' treatment window could lead to cancer therapy without harmful side-effects

Team members:

Melissa Call, Laboratory Head, BSc MSc PhD Auckland

Samyuktha Ramesh, Postdoctoral Fellow, BTech Anna Univ Chennai PhD Melbourne

Ashleigh Davey, Senior Postdoctoral Fellow, BBiotech(Hons) Monash PhD Melbourne

Jasmine Rou, Honours Student, BSc Melbourne

Julie Nguyen, Research Assistant, BSc(Hons) Monash

Margareta Go, Research Assistant, BMedSci Univ Applied Sciences Utrecht

Lincoln Smith, Research Assistant, BBiotech(Hons) PhD Newcastle