171P - Immune-modulatory drug profiling using perfused, microfluidic on-chip co-cultures of patient-derived ovarian cancer microtumors and autologous immune cells

Background

Ovarian cancer (OvCa) is one of the deadliest cancers in women, with a 5-year survival rate of about 40%. It is difficult to diagnose early due to the lack of specific markers and symptoms and exhibits high intra- and intertumoral heterogeneity, affecting individualized treatment responses. OvCa is typically detected post-metastasis and often recurs after standard care (SoC) therapy, necessitating new therapeutic approaches and insights into patient-specific treatment responses. Supported by Wellcome LEAP's HOPE program, a novel ex vivo platform combining OvCa patient-derived microtumors (PDM) and tailored organ-on-chip technology has been developed.

Methods

Protocols allow for the perfused on-chip culture of PDMs for 14 days with stable viability. The project focuses on immunomodulatory drug treatment profiling using on-chip co-cultures of PDMs and autologous immune cells. PDMs from six patients were pre-treated on-chip with or without taxane-based chemotherapy, followed by the addition of autologous tumor-infiltrating lymphocytes (TILs) and anti-PD-L1 immunotherapy at varying concentrations. Flow-through samples were collected daily over 14 days and tumor cell killing and cytokine/chemokine release were monitored. Immunofluorescence staining for pan-cytokeratin (tumor cells) and CD3 (T cells) provided insights into TIL migration and recruitment.

Results

To conclude, in on-chip PDM-TIL co-cultures from relapsed tumors, there was minimal response to pre-treatment chemotherapy and limited release of pro-inflammatory cytokines (granzyme, perforin). In contrast, PDM-TIL co-cultures from non-relapsed tumors showed substantial tumor cell killing and cytokine release after chemo pre-treatment. FACS-based phenotyping analyses focused on TIL activation and exhaustion status will be included. Additionally, further data from the same experimental setup with co-cultures of PDM with autologous PBMCs instead of TILs will be presented.

Conclusions

We successfully developed a perfused microfluidic chip platform enabling the parallel monitoring of patient-specific responses to different treatment modalities over extended periods.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

NMI Natural and Medical Sciences Institute at the University of Tuebingen.

Funding

Wellcome Leap HOPE Program.

Disclosure

All authors have declared no conflicts of interest.