Checkpoint inhibitor response prediction milestone using patient-derived ex vivo spheroids

12 Mar 2021
Checkpoint inhibitor response prediction milestone using patient-derived ex vivo spheroids

Researchers have demonstrated that their immune-modified ex vivo platform can measure treatment response through direct interaction between a patient's cancer and infiltrating immune cells, and immuno-oncology agents.

This work, published in the March 2021 issue of Cancer Immunology, Immunotherapy, validates the use of this platform in a pre-clinical setting to demonstrate tumour sensitivity to immune checkpoint inhibitors alone or in combination with other drugs.

Immunotherapy agents, although a potentially promising cancer treatment option, cost a premium and in many cases only 10-30% of patients respond to treatment.

Currently, there is a great need and opportunity to better predict which patients will respond to immunotherapies.

Patient selection is a challenge; the magnitude of this challenge has been validated by the recent withdrawal of approval of four immunotherapies for more than one cancer indication.

This study, which demonstrated that clinically relevant biological changes in immune cells and ovarian cancer cells could be detected in KIYATEC's platform after treatment with immune checkpoint inhibitors, marks significant progress towards successfully predicting immunotherapy response in the clinic.

Tessa DesRochers, PhD, KIYATEC Chief Scientific Officer said, "This paper highlights our ability to model the immune microenvironment of a patient, and then measure checkpoint inhibitor response alone or in combination with PARP inhibitors. Most checkpoint inhibitors are used in combination with other drugs and the PARP inhibitor combination is particularly relevant in ovarian cancer."

Past clinical studies demonstrated that the presence of immune cells in ovarian tumours generally leads to improved patient survival.

However, the use of checkpoint inhibitors such as pembrolizumab, which blocks the PD-1 receptor thus allowing immune cells to attack cancer cells, has not been successful in clinical trials.

In this study, primary ovarian cancer tissue was used to generate 3D spheroids, containing both tumour cells and infiltrating immune cells.

Before applying drug treatments, the researchers validated infiltrating immune cell function in the co-culture platform.

The spheroids were then treated with the checkpoint inhibitors durvalumab or pembrolizumab alone or in combination with olaparib, a PARP inhibitor.

Cancer treatment success is measured by tumour cell death. Strikingly, KIYATEC's platform showed that tumour cell death was due to the anti-cancer activity of the immune cells within the spheroids.

While these findings highlight the synergy between pembrolizumab and olaparib in ovarian cancer tumours that contain immune cells, the overarching excitement is the potential for platform use for the personalised, clinical prediction of immune checkpoint inhibitor response.

KIYATEC's platform is already predictive for chemotherapy and targeted agents. While studies will be performed to correlate the test results with patient immunotherapy endpoints in the clinic, today, pharmaceutical companies can use KIYATEC's platform to aid decision-making during drug lifecycles.

"Our platform has demonstrated the ability to generate responses across multiple therapies, including chemotherapies, targeted agents, and immuno-oncology agents. Also, the platform can tease out intricate biological interactions between tumour cells, immune cells, and therapeutics in ways that are not possible in patients. We believe that a test predicting patient-specific response with clinically meaningful accuracy reflects a multi-billion-dollar market opportunity," said Matthew Gevaert, PhD, CEO and Founder of KIYATEC.

Source: KIYATEC Inc.