ideasIdea
Grow tumour organoids together with the patient's own immune cells
Lab-grown mini-tumours usually contain only cancer cells. Adding the patient's own immune cells lets researchers test immunotherapy outside the body.
Air-liquid interface organoids and reconstituted co-cultures preserve or restore tumour-infiltrating lymphocytes and myeloid cells, and have been used to model checkpoint blockade responses and to expand tumour-reactive T cells. Standardising these systems, including autologous peripheral blood mononuclear cell co-cultures with defined killing readouts, would give an ex vivo assay for immunotherapy and cell therapy that plain organoids cannot provide.
Hypothesis
A standardised organoid-immune co-culture killing assay discriminates checkpoint inhibitor responders from non-responders in a prospective cohort with accuracy better than PD-L1 immunohistochemistry.
Rationale
Immunotherapy prediction is the field's most valuable unmet biomarker problem and functional assays outperform expression markers in other settings, such as ex vivo drug sensitivity in leukaemia.
What would test it
Assay 150 pre-treatment samples from patients starting checkpoint therapy with blinded scoring; compare accuracy with PD-L1 and tumour mutational burden.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks
- Preclinical models that do not predict people · Nine in ten cancer drugs that work in mice fail in humans. Our models are the reason.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.