Interview with Cancer Researcher Dr Ali Roghanian

Tell us about your current research focus and why did you decide to focus your career on that particular area of research?

I have always been interested in biomedical research with the ultimate aim of helping patients who are suffering from cancer and thrive to see the impact of my basic scientific research in the clinic (translational research). Cancer affects a significant proportion of population and is a major cause of mortality. Despite many advances in recent decades, many patients fail to respond to approved therapies or unfortunately develop resistance down the line. As such, novel treatments are urgently needed to treat a wide range of cancer patients who currently fail to benefit from the approved therapies. By combining my expertise in immunology (which studies the immune system) and preclinical models, I have dedicated my scientific career to study the cross communication between the tumour cells and cells of the cells of the immune system.

This will help provide further insight into targeting of such pathways with novel drugs, to generate an effective and long-lasting immune response against cancer. Specifically, I am interested in generated antibody drugs that can be used to reprogram the immune system against the tumour cells, a class of treatment that has been very effective against several cancers (cancer immunotherapy), i.e., your own immune system will detect and identify the cancer cells and destroy them.

How could your research change the way cancer is treated?

Cancer immunotherapy is a powerful class of treatments that has the potential to generate potent and long-lasting immunity against tumour cells, like providing protection against viruses and bacteria. Similar to vaccination, the potential of cancer immunotherapy to induce memory immune responses is of particular importance, as it limits the chance of tumour recurrence and escape. Moreover, compared to conventional cancer therapies (e.g., chemotherapy), cancer immunotherapy has fewer side effects and can be personalised based on the patient’s status and their cancer subtype. In this way, the patient’s natural immune system will be trained and programmed by drugs, such as antibodies, to patrol their body and identify the cancer cells. Once the cancer cells are detected, then the immune cells will be able to attack them and result in their death. Not only this is effective in short-term, it can also produce a long-lasting memory, thereby preventing cancer cells hiding in the body and coming back in the future.

You’ve just received funding from Breast Cancer Now for a new study, please explain what the study aims to do and what impact it could have?

Breast cancer is a devastating disease which effects so many people across the UK and beyond. Despite advances in treating breast cancer a considerable number of patients are still difficult to treat and do not respond to usual treatments. This is devastating for those patients affected. My research will help to understand the mechanisms via which these cancers bypass the patients’ natural immune system and will investigate why they do not respond well to the usual treatments. By doing this we can then target and develop new therapies for this group of patients. Specifically, through this study we aim to target a negative feedback loop between the tumour cells and myeloid cells (a type of immune cell which is abundant in the tumour and support tumour growth and metastasis) to overcome resistance to chemotherapy. These data will provide better understanding of the common mechanisms involved in suppressing the immune system in therapy-resistant breast cancer patients, and will, ideally, translate into future treatments in the clinic. We hope our findings will benefit a wide range of patients with various subtypes of breast cancers, in particular those of more aggressive nature and hard-to-treat, such as Triple-Negative Breast Cancer. I am very grateful to the Breast Cancer Now charity and their very many generous donors for their generous support.

As you know the Centre was funded entirely through philanthropic donations and the Cancer Immunology Fund continues to fund our research and train the next generation of researchers. As a scientist, how important is to have such support for medical research?

Cancer Sciences at the University of Southampton has a long history of making innovative discoveries which have directly contributed to the treatment of cancer patients, going back to the 1960’s, when first immunotherapies were successfully tested in local patients. But doing basic research is very costly and requires the latest technological advances and experimental models in order to generate effective therapies. This could have not been achieved without such generous donations. As a group leader and scientist working in the Centre for Cancer Immunology, I am extremely grateful to the generous philanthropical donations that have made it possible to establish a world-class centre focused on cancer immunotherapy in Southampton.

The Cancer Immunology Fund is fundamental in supporting the more junior members of the Centre, including myself, as they provide the basis to generate the proof-of-concept data required to attract more substantial fundings from the governmental (eg, MRC) and cancer charities (eg, CRUK).

The Cancer Immunology Fund is fundamental in supporting the more junior members of the Centre.

What do you think the future holds for cancer immunotherapy?

Over the last few decades, immunotherapy has expanded into vast areas of medicine, including the treatment of cancer, autoimmune conditions, infectious diseases, allergy, and inflammatory disease. This included antibodies and well as engineered cell therapies, such as CAR T-cells. Thanks to these new treatments, many cancer patients, whom would have previously only lived for a few months post diagnosis, are now tumour-free and enjoying a normal life. This is a remarkable achievement, and it is expected that, as more classes of immunotherapies get approval, more and more patients will benefit from their effect on a personalised basis, with little side effects. We are at the forefront of this research and we anticipate a number of our translational research to significantly improve cancer patient therapy in many years to come. We benefit from our ideal location, based at the Southampton General Hospital and from the Southampton Clinical Trial Units that is located at the Centre, helping test our novel therapies in patients.

What would you say is your proudest career achievement?

The ultimate aim of our research is to help treat cancer patients, and it is every scientist’s ambition to able to translate their research into effective therapies in the clinic. However, doing basic research is extremely time consuming and very costly. Unfortunately, most often the basic research fails to translate into meaningful treatments in the clinic. My proudest achievement is being closely involved in a project developing a new class of immunotherapy, that is currently being trialled to treat patients with solid and haematological malignancies. This is a unique achievement and a dream come true!

In collaboration with a Swedish biotech company (BioInvent International), I previously helped characterise a panel of human FcγRIIB (CD32B) antibodies and explored the therapeutic potential of targeting FcγRIIB in preclinical models. Several of these antibodies showed anti-tumour activity; one of which was chosen as a clinical candidate showed promising single agent activity in our preclinical models. Importantly, and in agreement with our preclinical studies, the lead candidate (BI-1206) has recently been shown to have a promising safety profile in patients and the early clinical trial results have been highly encouraging, with a number of Non-Hodgkin lymphoma patients achieving partial and complete responses. Due to its early promise and effectiveness against refractory/resistant lymphoma, BI-1206 has also received FDA Orphan Designation for mantle cell and follicular lymphoma.

Similarly, another clinical candidate that was selected by the team is now in clinical trials for the treatment of patients with solid cancers.

I sincerely hope that by continuing to generate new drugs to target difficult-to-treat cancers, we will be able to fully eradicate as many cancer types as possible and ultimately extend the life expectancy of patients affected by cancer.