The Development of a Novel Therapeutic Strategy to Treat Advanced Prostate Cancer:

Using Mesenchymal Stem Cells to deliver TRAIL to Prostate Cancer Tumours



Prostate cancer is the most common cancer in men in the UK with more than 46,000 cases diagnosed per year. The growth of prostate cancer is dependent upon the male sex hormone androgen. Treatment options, for tumours that have spread from the prostate capsule, therefore include methods to inhibit androgen production (LHRH analogues e.g. Goserelin) and action (antiandrogens e.g. Bicalutamide). These therapies are successful in the majority of patients, but some tumours progress to the castrate resistant stage. We are developing novel treatment options for this stage of the disease.

Therapy resistance is a major clinical obstacle in the management of prostate cancer. Prostate cancer cells often undergo changes which protect them from cell death, making them resistant to anti-tumour drugs.

We are extremely grateful to Prostate Cancer UK for giving us a Research Innovation Award to develop a novel strategy to treat therapy-resistant prostate cancer.

The Research Outline

We have discovered a novel way of attacking and killing prostate cancer cells by combining the effect of stem cells and of a naturally occurring protein called TRAIL. TRAIL causes cancer cells to die and re-sensitise tumours to treatment. Importantly, TRAIL has been shown to cause tumour death specifically, leaving normal healthy cells and tissues unharmed, thus reducing the risk of side-effects. TRAIL is unstable when injected and hence the difficulty has been in how to deliver this protein to patients.

To solve this limitation, we have been loading mesenchymal stem cells (MSCs) with TRAIL and using them as a “Trojan Horse” to deliver this protein to the tumours. Although this approach is likely to be an effective therapy for all types of cancer, it is of particular relevance to prostate cancer, because MSCs are able to seek out primary tumours as well as those that have spread/metastasised to other tissues such as bone.

Our therapeutic strategy utilises the ability of Mesenchymal Stem Cells (MSCs) to circulate and infiltrate primary tumours as well as cancer cells that have spread to other parts of the body (called metastases). We will load these MSCs with a modified version of TRAIL.

Our previous results demonstrated the feasibility of TRAIL-based therapies for cancer, but also highlighted that most tumours are best fought with a combination of two or more drugs including cellular therapeutics such as our MSCs. Therefore we will also include other prostate cancer drugs (e.g. Docetaxel), with the aim of achieving greater tumour death.

We will test our therapeutic strategy on cell-line models and tumour samples from prostate cancer patients to identify the optimal TRAIL and drug combination. Following this optimisation, we will use preclinical models of prostate cancer to confirm the safety of our therapeutic approach and demonstrate that this treatment can effectively kill cancer cells. Clinical trials using a similar approach are underway for the treatment of lung cancer. Hence, following the additional preclinical tests proposed here, it will be feasible to initiate clinical trials using MSCs loaded with TRAIL for advanced prostate cancer.

An important feature of MSCs is that they are recruited to damaged tissues in response to “danger signals” emitted from the sites of injury. Arriving at these sites, the MSCs normally contribute to the repair of the tissue. As tumours also produce these “danger signals”, MSCs are also recruited to tumour sites and can deliver cancer cell-killing payloads. We have already shown the potency of our therapeutic approach in models of human pancreatic and colon cancer.

Our strategy has significant advantages over more conventional approaches: i, MSCs will circulate through the body and seek out and infiltrate primary tumours and metastatic sites (for example bone metastases); ii, the specially modified TRAIL used in this study is more potent, because it promotes cancer cell death in a larger population of cells. Now, we would like to further test, develop and optimise the MSC-based TRAIL delivery system for prostate cancer and aim to collect the necessary data to initiate clinical trials soon after project completion.

Therapy resistance is a significant issue for the clinical management of prostate cancer. Our MSC-based TRAIL delivery system, used as a stand-alone therapy, or in combination with conventional treatments, offers a novel targeted approach for this advanced aggressive stage of the disease.

It is envisaged that this strategy will overcome treatment resistance, cause tumour cell death and/or reduce the effective dose of conventional therapies (e.g. Bicalutamide/Docetaxel). This should therefore reduce adverse side effects, whilst improving survival rates and the quality of life for men with advanced prostate cancer.

At the end of year 1 we will have identified the best modifications, optimisations and combinatorial treatments for our MSC-TRAIL biotherapeutic. During the following 2 years, we will use preclinical models of prostate cancer to demonstrate the safety and potency of our therapeutic. At the end of the project we will have generated the data needed to support clinical trials in prostate cancer patients.

We will be collaborating with clinical partners and biotherapeutic manufacturers, who can produce the components at clinical grade quality. This will ensure swift progression of our therapeutic into human trials shortly after project completion.


Prostate Cancer Research at Essex University 

Meet the research team - from left to right:



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Dr Ralf Zwacka and Dr Greg Brooke
School of Biological Science
University of Essex

© Prostate Cancer Research School of Biological Science University of Essex CO4 3SQ

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