Research Update – September 2021
Things have been slow to progress as we are still rebounding from the pandemic - seems flus and colds are coming back with a vengeance! The flow sorter has also caught a bug and so sorting the Queen bees has been interrupted! We are ploughing through though. Jamie is doing a great job under the current circumstances, is finalising experiments for his PhD thesis and we hope to have the next manuscript ready for publication soon - the priority is getting the Queen bee work published now. Jamie is working with Chris on this, they are working well together and Jamie has trained Chris on the techniques needed for the project.
I have also been asked to lead the biology for the upcoming ACCELERATE Glo-BNHL clinical trial (https://www.accelerate-platform.org/2020/09/10/glo-bnhlan-opportunity-pharma/) which means we will have more access to samples for our research.
The Glo-BNHL trial is for children that have relapsed with B-NHL across the world and will be a real change in the way we treat children in the future. It is very exciting to be involved in this. Cancer Research UK (CRUK) and Kick Kids Cancer have now agreed to fund the clinical trial. The Little Princess Trust has also supported us now with £250,000 for the biology associated with the trial. We hope the trial will be able to start towards the end of 2022 and will run for 7 years. It's very exciting to be moving ahead with this.
In other news, we are now advertising for new PhD students to take part in the CRUK Cambridge centre graduate training programme. Our project on childhood B cell lymphoma has been selected as part of this programme. If we are lucky enough to get a student through this programme, they would work alongside Chris and Jamie - the more hands on deck the quicker we can progress. So it is a side-step from Alex’s project that would not have been possible before.
Research Update – June 2021
Things are very slowly returning to normal following the shut-down due to the pandemic; the lab is now open at 25% occupancy and so the guys in the lab are having to work shifts and coordinate so that there are never more than 2 in the lab at a time! Jamie is very happy to be back in the lab! Unfortunately, the whole COVID has situation set us back a fair bit, but I am sure we will be back up to speed in no time.
We have now submitted the first manuscript from Sorcha’s PhD work to the British Journal of Haematology. Now we have to wait to see if they like it, if they do, they will then send it to 2-3 people for peer review which can take a month. The editor then decides if they want to publish it. This paper is the ‘prequel’ to the main paper from Sorcha’s thesis (the Queen bees), as we decided there was too much work for one article and with this one, we want to advertise to the scientific community that we have developed this valuable resource. The second paper is being written as data are produced and once Jamie has undertaken a few more experiments to finish off the work it will be ready to go. Jamie is due to finish his PhD in February (10th) which will be the 4-year limit allowed at the University of Cambridge.
We have also been able to secure a funded PhD student to work with Jamie in the lab, his name is Chris Steele. I am really pleased that we will be able to continue with our research in the name of Alex. The Foundation has kindly agreed to fund consumables costs for Chris so he can continue with the work after Jamie has finished his studies. Chris with pick up from where Jamie has left off.
Update from Jamie
We have initiated a new collaboration with a group in Germany who read Sorcha’s paper and recognised the utility of the PDX model - I will be using it to test a potential new drug which they have identified to be highly effective on B-NHL cells when they are grown in petri dishes. Sorcha is working on writing up more of her findings for publication, and my contribution to that will be extending findings from cell line experiments to patient cells and comparing the transcriptomes (how the DNA code is interpreted by the tumour cells) of the Queen Bees and the rest of the tumour - RNAseq data of the transciptomes that I analysed over the lockdown hinted at differences in metabolism of the Queen Bees, which I hope to confirm when we are allowed access to the cell sorters following lockdown.
I have been working on using the PDX for mini personalised drug trials in cell media for relapsed patient tumours and so far, we have shown that our model captures the patient’s initial response to their treatment. Further, in many cases I found that an alternative drug was able to clear the tumour where the original treatment failed, and I am currently putting together a new paper with a colleague to share these data with the community. Some recent evidence from other cancers has suggested that the timing and rhythm of drug treatment can have an impact on tumour growth separately from the drug itself, potentially presenting a path to not only better control of the tumour, but also to do so with a lower overall dose, reducing the devastating side-effects of even successful treatment. Our PDX models are a perfect platform to test that idea, and I’m very keen to get this underway and link tumour behaviour in cell media to the underlying genetics of the patient.
I am extremely grateful for the opportunity to work on such an important and fascinating area, as well as to develop my knowledge as a student and skills as a scientist. I have learned a huge amount from Suzanne and the lab and have progressed from needing constant supervision to doing a little supervision myself. Having hugely enjoyed my time in Suzanne’s lab, and looking forward to my final year, I’ve decided to stay in research when I’ve finished my PhD. It’s an exciting time - recent trial results show survival rates in adults and children are increasing, and news that a new trial will be conducted in the UK specifically for children with relapsed B-NHL is extremely welcome, if long overdue.
Alex Hulme Foundation PhD Student – 2017 to 2022
Research Update – February 2021
Dear Supporters and friends
It has been a while since we last reported on our progress and so much has happened in between! As is the case for many, our research has been badly affected by the COVID pandemic. Back in March 2020 we had to close the lab, down tools and stop all experiments. Whilst we have since returned to the lab, things are far from normal with members of the lab working in shifts so as to maintain social distancing. We have also had to catch up on things, regrow cell cultures and are only just now getting back to some relative normality and producing results. Unfortunately, despite no travel and working from home, I am busier than ever but have recently been reflecting on what we have achieved in the past 9 years of our work with the Alex Hulme Foundation.
In 2017, Jamie Matthews, an Oxford graduate with a Masters degree in immunology (the study of the immune system) joined the lab as the second Alex Hulme Foundation PhD student. Jamie has taken over the project from Sorcha and has made fantastic progress in identifying the drug sensitivities of the Queen Bees. He has also been analysing sequencing data comparing the genetic sequence of tumours before therapy in comparison to when they have become resistant. This work has highlighted some potentially new drugs for the treatment of children, like Alex, with relapsed B-NHL (please see Jamie’s update below). We are currently assembling these data into a manuscript that will be published in the clinical and scientific literature soon. Jamie has 1 year left to complete his PhD studies, write his thesis and be examined; I have every confidence that he will be successful.
This brings us to the future and the hope that it will not be too much longer before we can return to some form of normality. We are excited to be involved in a new clinical trial called Glo-BNHL that will operate around the World. This trial will be for children with relapsed B-NHL for which we will be coordinating the biological studies. As such, the trial will give us the opportunity to help more children with relapse/refractory B-NHL. In particular, this trial will focus on a relatively new form of cancer treatment called immunotherapy. This involves engaging the immune system of the patient to recognise and kill the tumour cells. We will be developing avatars of the patients enrolled to the trial so that we can monitor their treatment response in real time. In particular, we will be using an innovative approach using media that have a human immune system to mimic immunotherapy and determine potential resistance mechanisms. However, first we need to secure funding for this research and we thank you all for your continued support for which we are extremely grateful.
Hopefully, it will not be too much longer before we can meet up again in person to celebrate our achievements and of course, to remember Alex.
Dr Suzanne D. Turner PhD.
DEPARTMENT OF PATHOLOGY,
DIVISION OF CELLULAR AND MOLECULAR PATHOLOGY
UNIVERSITY OF CAMBRIDGE