Story | 08/04/2021 10:08:27

Model development for ex vivo precision oncology

Precision medicine in oncology aims to provide targeted treatment for individual cancer patients, but current technologies for assessment of cancer therapy lack patient- and tumor-specific predictive information of treatment efficacy. There is an international effort to discover empirical evidence of treatment effectiveness for individual patients, with many researchers – such as those at Misvik Biology in Finland – turning to ex vivo screening approaches that use patient-derived tumor cells as models to determine the best treatment for any solid cancer type.

Dr Juha Rantala, CEO and founder of Finnish biotech company Misvik Biology, is working towards the development of novel technologies for high throughput drug screening. Since the company was founded in 2014, Misvik Biology has supported both academic research groups and pharmaceutical companies to assist them in detecting target molecules of interest and assessing therapies for pathologies, including various rare solid cancers. The company has fostered a number of collaborations, including a joint clinical development program with the University of Sheffield, and a preclinical research collaboration with UPM Biomedicals.

The goal of these partnerships is to clinically validate an ex vivo therapy efficacy screening strategy that compares the sensitivity of an individual patient’s tumor cells to 150 approved cancer drugs in one test. This method allows assessment of patient- and cancer-specific responses, highlighting those treatments that could result in the most clinically favourable response. Juha explained: “Misvik Biology has grown substantially since it began, and we have made significant progression in the development of ex vivo models for drug screening. Since June 2019, I have worked with the University of Sheffield and Weston Park Cancer Centre – a leading site for bladder cancer research in the UK – and we are now starting Phase 1 clinical trials to perform clinical validation of our technology in the context of bladder cancer. This high throughput screening method can assess therapeutic efficacy for hundreds of drugs targeting cancer cells in parallel, but we are also working on 3D cell-based models to assist with translational research for bladder cancers.”

“Muscle invasive forms of bladder cancer are highly aggressive, and can quickly grow and metastasize, spreading rapidly around the body. This makes it critical that patients are promptly diagnosed and provided with effective treatment to gain the most favourable clinical response. There are currently limited therapeutic options beyond the standard chemotherapies approved for bladder cancer, making the selection of the optimal standard treatment ever more important. Using our screening approach, it could be possible that the best treatment decision is made for each patient first time. When bladder cancer is diagnosed, the tumor is routinely sampled during transurethral bladder resection. The whole tumor will be removed in this procedure, and the leftover tissue from the routine pathological assessment can be used for testing with the techniques that we are developing.”

The labs within this collaboration are working in the Yorkshire area of England, and aim to recruit 400 bladder cancer patients to the study over a four-year period; biopsy samples will be taken from these patients, analyzed with the ex vivo drug screen, and cultured using both standard 2D cell culture and in 3D conditions using GrowDex® hydrogel. Juha continued: “As we grow the patient samples under these different conditions, we will be able to compare the tumors’ growth pattern in the different cultures side by side, to see if using GrowDex for ex vivo propagation of tumor explants is more efficient. This will be important to establish how we can best maintain patient-derived tumor samples ex vivo.”

“We have been working with UPM for around five years. Before this collaboration, we were one of the first research groups in the world to demonstrate 3D cell culture of human prostate cancer models. Now, we are performing studies on primary prostate cancer cultures using GrowDex hydrogels. What’s interesting about using GrowDex is that human cells do not stick to it; they are forced to maintain growth in suspension within the hydrogel. This is ideal when looking at certain cancer subtypes that grow in suspension in the body. Many of these cancers are neuroendocrine small cell cancers derived from different epithelial tissues – including bladder, prostate, pancreas, lung and colon – and often represent the most aggressive subtypes. Using GrowDex to grow these cancers ex vivo means that we can mimic the conditions for rapid tumor growth, and obtain results that are representative of what’s going on in the body – it’s a crucial part of developing a better understanding of these cancers, and finding cures for patients.”

“Our feasibility studies have been successful so far and, as we continue to progress, we are always looking to collaborate with additional international groups. We are already working on these projects with multiple sites in the UK, as well as several hospitals in Finland, and are looking forward to where this technology can take us in the future, to further both the biotech industry and precision oncology.”


GrowDex® Hydrogels

High throughput screening