191P - Patient-derived 3D-bioprinted tumours as a relevant and innovative tool for immunotherapeutic testing.

Background

Carcinotech's 3D bioprinted tumour models offer a transformative platform for advancing cancer drug screening and therapeutic testing by accurately replicating the complexity of the tumour microenvironment (TME). Unlike traditional 2D cultures, organoids, or animal models, these bioprints incorporate multiple cell types from patient-derived cancer tissues in a robust tissue matrix, providing a more biologically relevant model for preclinical studies, particularly in immuno-oncology and personalised medicine. Our recent research shows that these models effectively represent the presence of tumor-infiltrating lymphocytes (TILs), a crucial immune cell group targeted by advanced immunotherapies.

Methods

Patient ovarian tumour biopsies were sectioned, processed into FFPE blocks and TME characterised using immunofluorescence (IF) technique. Patient-derived cells were cultured as a heterogeneous population and 3D-bioprinted with custom bioink onto 96-well plate format. After 14 days in culture, characterisation of 3D-model TME composition was performed to compare it to the original tumour to assure high TME representation. Additionally, Carcino3D ovarian cancer models were treated with well-established immunotherapeutics Pembrolizumab and Rituximab, and activation of immune markers using IF as well as pro-inflammatory release of Granzyme B post-treatment tested.

Results

While the viability of the Carcino3D tumour model slightly declined after treatment, we observed stronger immune responses, including cytokine release, when treated with Pembrolizumab or Rituximab. Through advanced 3D imaging and AI-based analysis, we identified an increase in T-cell numbers post-treatment. Interestingly, early-stage T-cell activation decreased, while late-stage activation markers increased, confirming the models' accuracy in predicting therapeutic outcomes.

Conclusions

These findings highlight the potential of Carcinotech's 3D bioprinted models to significantly accelerate immunotherapy research and improve drug development pipelines. By offering a more dynamic and representative testing platform, these models promise to reshape the future of cancer drug discovery and personalised treatment approaches.

Legal entity responsible for the study

Carcinotech Ltd.

Funding

Carcinotech.

Disclosure

K. Pawlicka, M. McDonald, B. Kennedy, V. Metodieva, J. Adams: Financial Interests, Institutional, Full or part-time Employment: Carcinotech.