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Could the immune system hold the key to curing follicular lymphoma?

Professor Maher Gandhi leads the first research group in the world to investigate a new therapeutic approach for follicular lymphoma (FL) that includes harnessing a patientโ€™s own immune system.

Professor Maher Gandhi
Professor Maher Gandhi

โ€œWe need a new way of looking at things,โ€ said Professor Gandhi, who was recently appointed CEO of Mater Research (Brisbane).

While several groups around the world are looking at the properties of cancer cells, his Brisbane-based research team is โ€œspending a lot of time on the properties of the immune cellsโ€ in FL.

And heโ€™s expecting โ€œa big breakthroughโ€ later this year for this research project that recently was awarded funding of $200,000 as part of the Leukaemia Foundationโ€™s National Research Program*.

Trying to cure an incurable subset of FL

Prof. Gandhiโ€™s interest in follicular lymphoma โ€“ the second most commonly diagnosed form of lymphoma โ€“ is both personal and professional.

โ€œA lot of my patients have this [FL] and I find it very challenging that we canโ€™t cure them, so itโ€™s always been a passion of mine to try and cure it,โ€ said Prof. Gandhi.

โ€œWe can cure FL in a small subset, and to try and extend that to a bigger subset is something I feel very motivated by.

โ€œThere also are particular features of this lymphoma, from a scientific point of view, that have always intrigued me. And Iโ€™ve always believed FL was a cancer influenced by the immune system.โ€

FL occurs in older patients and there are two kinds. In 15-20% of cases, the FL is โ€œvery isolated in a small group of lymph nodesโ€. For the other 80-85% of cases, โ€œitโ€™s more advancedโ€.

โ€œWhatโ€™s interesting is that in the small group, it seems FL is curable in a proportion of them, but in the other patients, itโ€™s incurable โ€“ it can be treated and controlled but it comes back, and it never goes away,โ€ said Prof. Gandhi.

โ€œWhat we want to do is look at that small group and find out what the molecular features are that actually means that it can go away. Our data so far suggests itโ€™s due not so much to the biology of a lymphoma cell, but the surrounding immune cells.

โ€œIn some cases, those immune cells are very common, and these patients do much better. In other cases, the immune cells are hardly there at all, and they do much worse.

โ€œIf we can confirm this, itโ€™s quite important, because it might suggest that the best way to treat FL is to profile the tumour at diagnosis and in cases where very few immune cells have infiltrated the lymphoma, we could possibly design new therapies that actually cause the immune cells to infiltrate the lymphoma.

โ€œMaybe we should be using the patientโ€™s own immune system to help fight their lymphoma,โ€ said Prof. Gandhi.

โ€œWeโ€™ve looked at a group of Brisbane patients, have confirmed our findings with groups internationally, and now weโ€™re trying to confirm the findings in larger groups of patients including a group of patients from a clinical trial.

โ€œThis involves working with investigators at the Peter MacCallum Cancer Centre (Melbourne).โ€

A new approach

Prof. Gandhi explained that some patients with FL are treated with chemotherapy, some with antibody therapy, some have radiotherapy, and some get all three.

โ€œWe donโ€™t know which is best, or what combination is best, but we do know that even by giving all three therapies, there are some patients who arenโ€™t cured.

โ€œSo whatever we do, itโ€™s not ideal. We need a new way of looking at things which is why weโ€™ve taken the approach we have, because it suggests that we need a new approach that harnesses the patientโ€™s own immune system as well.

Prof. Gandhi said initial funding for this research, from the National Health and Medical Research Council, was very important.

โ€œIt meant I could finally do that [comprehensively analyse early stage FL], but the monies were never enough to answer all the questions, so the additional funding from the Leukaemia Foundation will really enable me to address this properly and more rapidly,โ€ he said.

โ€œIt will be used to appoint a post-doctoral researcher to work on this project for two years, starting in July.

โ€œBecause we had already started work with the NHMRC funding, weโ€™re going to have some results this year.

โ€œOur work is very advanced. Our results are very interesting indeed. We are quite excited by the findings.

โ€œI expect weโ€™ll get our big breakthrough this year,โ€ said Prof. Gandhi.

โ€œWeโ€™re hoping to show that we can identify people who are more likely to do badly and that it is related to their immune system. And our work might be the basis of a clinical trial in which we could test this.โ€

*This funding is part of the Leukaemia Foundationโ€™s Strategic Ecosystem Research Partnerships (SERP) and was made possible thanks to generous individual supporters and the estates of Beverly Simersall and Dorothy Ruth Forest.


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