The idea of cancer vaccines is not new, but Dr Victoria Kunene, consultant medical oncologist at Queen Elizabeth Hospital Birmingham, UK, is leading the charge in their latest iteration: personalised preventative and therapeutic mRNA vaccines against colorectal cancer. With an introduction from Helena Beer, Dr Kunene shares first-hand insights into the clinical trial, the NHS Cancer Vaccine Launch Pad initiative and their potential for revolutionising patient care.
Ask Dr Victoria Kunene why she wanted to specialise in oncology and her answer won’t be too dissimilar to the one she gave 15 years ago interviewing as a registrar: it’s the opportunity to help a unique patient group navigate an extremely challenging period in their lives and, where possible, give them extra time to spend with loved ones and achieve their goals.
‘Just being part of that journey and helping someone through a difficult time is humbling,’ she says. ‘It’s not easy, but it’s satisfying. You feel like you have positively contributed at a crucial time.’
While Dr Kunene’s drive, empathy and ambition have remained constant during her career, one thing that’s changed during the intervening years is the means by which she is able to help due to a ‘constant stream of new information and new treatments’ coming through the clinical development pipeline.
‘Treatment has advanced since my oncology registrar years – we’ve made some progress,’ she confirms. ‘Everyone would probably blow their trumpet about their own field, but [oncology is] the one field whereby science meets clinical practice so completely.’
Taking up a consultant medical oncologist post at Queen Elizabeth Hospital Birmingham (QEHB) in 2012, Dr Kunene now specialises in upper and lower GI cancers, and cancers of unknown primary. She has taken the lead on multiple clinical trials as principal investigator to continue satisfying her passion for marrying science and clinical practice.
On 31 May 2024, Dr Kunene led a team to administer the very first personalised vaccine against colorectal cancer in England as part of the pioneering NHS Cancer Vaccine Launch Pad (CVLP) initiative.
The overarching aim of this is to speed up access to messenger ribonucleic acid (mRNA) personalised cancer vaccine clinical trials for people who have been diagnosed with cancer to support treatment alongside chemotherapy, as well as prevention.
Speaking at the time of the CVLP launch, NHS chief executive Amanda Pritchard said: ‘Thanks to advances in care and treatment, cancer survival is at an all-time high in this country, but these vaccine trials could one day offer us a way of vaccinating people against their own cancer to help save more lives.’
Working to achieve this ambition is something that Dr Kunene is proud to be a part of, especially as it has the potential for allowing her to offer patients that all-important extra time.
How has the treatment of upper GI cancers changed during your time as a clinician?
When I started as a registrar 15 years ago, we only used chemotherapy but there were clinical trials in the background where we investigated targeted therapies like trastuzumab (brand name Herceptin) for upper GI cancers. I remember recruiting patients into the ToGA trial and now to see trastuzumab as part of standard of care for HER2-positive upper GI cancers is great.
Of course, we’ve also had the advent of immune checkpoint inhibitors. These immunotherapies are now part of standard of care with or without chemotherapy for patients who have PD-L1 positive or microsatellite-high tumours.
Another treatment combination is chemotherapy with zolbetuximab – an antibody directed against claudin 18.6. Although the QEHB didn’t take part in the related study, our neighbouring hospital of University Hospital Coventry and Warwickshire did, and the results are positive. Zolbetuximab received Medicines and Healthcare products Regulatory Agency approval in August and is currently undergoing review by the National Institute for Health and Care Excellence.
And what about treatment advancements in lower GI cancers?
In lower GI cancers, we regularly conduct tests for RAS and BRAF mutations, mismatch repair proteins, NTRK gene fusions and HER2 amplifications. This allows us to utilise appropriate antibodies such as anti-epidermal growth factor inhibitors, immunotherapy, trastuzumab and larotrectinib to positively impact clinical outcomes.
Other drugs like bevacizumab and aflibercept, which are vascular endothelial receptor inhibitors, do not require genomic or immunohistochemistry testing. In suitable cases, these are administered in combination with chemotherapy.
Interestingly, we also see advocacy for old drugs like aspirin, which could improve outcomes in certain groups of patients. Over the years, various study groups have reported improved survival with the use of aspirin and other non-steroidal anti-inflammatories. Thus, it’s not only about new drug discoveries but leveraging current technology to optimise the use of old drugs.
We have witnessed the advancement of radiotherapy with new techniques like stereotactic body radiotherapy, which enables clinicians to deliver high doses of radiotherapy with precision and reduced toxicity. Surgeons are performing more intricate procedures, leading to longer survival for patients due to the increased use of combinations of treatment methods.
We are currently in the era of stratified medicine, where genomic sequencing, circulating tumour DNA, prognostic scoring systems and predictive artificial intelligence models are being optimised so they can be incorporated into routine care to improve survival and reduce treatment toxicity.
How do you see personalised cancer vaccines – and the colorectal cancer vaccine trial you’re leading – fitting into this treatment landscape?
The idea of cancer vaccines is not new, but previous studies were not very successful, especially in metastatic settings. Following the Covid-19 pandemic, we have seen increased research into personalised mRNA anticancer vaccines and, so far, early phase studies have shown promising results.
Of course, there are other types of vaccines available such as DNA-based vaccines, peptide-based vaccines and dendritic cell vaccines, which are also being investigated in various tumour groups.
The study that we’re doing is in high-risk, stage two and stage three colon cancers. In these patients, especially the stage three cancers, 20-30% will experience cancer recurrence despite receiving post operative chemotherapy.
For a very long time, we relied on CT scan staging to decide which patients would benefit from chemotherapy, however this method is not reliable.
In the last five to 10 years, there’s been more work in the area of circulating tumour DNA and minimal residual disease in solid cancers. Haematology has always been at the forefront of this, and they have always considered minimal residual disease in their treatments.
We know from recent literature – even just observational studies – that patients who have detectible circulating tumour DNA after the removal of their cancer are at a high risk of cancer reoccurrence. Therefore, this study concentrates on this group of patients.
What does the trial involve?
We offer the patients participation in the study when they attend for consideration of post-operative chemotherapy. If they agree to have both the chemotherapy and the clinical trial, we do screening blood tests for circulating tumour DNA at least four weeks post-surgery, but no later than 10 weeks, as treatment must start within 10 weeks of surgery and not a day later.
Blood tests take a few weeks to become available, so patients continue with their standard post-operative chemotherapy, which could be for three or six months. The results could be either positive or negative for circulating tumour DNA and sometimes the test fails. This is screening phase one.
Screening phase two is for patients who test positive for circulating tumour DNA. If they are happy to continue the study, they will sign a second consent form to allow the study team to manufacture a bespoke vaccine by sequencing the tumour and identifying appropriate neoantigens. A minimum of five and up to 20 neoantigens are required to successfully manufacture the vaccine. These neoantigens are interrogated through a computer algorithm to assess if they can elicit the desired anticancer immune response.
If the neoantigens meet the requirement, the vaccine is then manufactured and can only be given to that particular patient.
What we’re trying to do with the vaccine is re-educate the immune system by generating specific T-cells against the cancer, thus giving the person a fighting chance. Vaccines are normally preventative – we vaccinate against measles, TB, rubella – but these vaccines are not just preventative, they are also therapeutic. If the cancer resurfaces, the immune system should be able to recognise it and get rid of it.
Screening phase three involves randomising these patients to receive their personalised vaccine – or not. How do you support both cohorts?
This phase involves blood tests and CT scans at the end of chemotherapy. If the blood results are satisfactory, there is no evidence of cancer recurrence and the vaccine has been successfully manufactured, the patient can be randomised.
Half of the patients will receive the vaccine, and the other half will be observed, which is the standard of care. If a patient is randomised into the vaccine arm, they will receive treatment once a week for the first six weeks, once every two weeks for a month and then every four to six weeks for up to 15 doses over the course of a year.
The vaccine made for the patients who don’t receive it will be destroyed and the ‘blueprint’ used to create the vaccine will not be used for other participants.
Patients who are randomised to standard of care are likely to be disappointed. We warn our patients that they might not get the vaccine. However, we highlight the benefit of receiving much closer monitoring [within the clinical trial] than the usual standard of care protocol.
We conduct blood tests and CT scans more frequently than usual, which increases the chances of detecting cancer recurrence earlier and taking prompt action. We also emphasise that the product is still being studied so we cannot predict the outcome.
How does the Cancer Vaccine Launch Pad fit into this?
The CVLP is a collaboration between NHS England and companies delivering this cancer vaccine technology. The aim is to be able to allow patients across the country to access these vaccine trials. Oxford was the first site to open the CVLP and we received their first patient.
QEHB is one of the vaccine delivery study centres. I also work at Walsall Manor Hospital, a district general hospital, with the CVLP. We [the Walsall team] approach suitable patients based on histology staging. If they agree, we will see them at the QEHB for the circulating tumour DNA screening blood test after signing the consent form. Then, they start chemotherapy at Walsall Manor Hospital, and we inform them of their results as soon as they become available. If they are deemed suitable for the study, they will undergo screening phases two and three if they are still happy to proceed.
One or two hospitals around Birmingham are not part of the CVLP and they also refer patients. Therefore, patients can still access the studies even if their hospitals don’t have the CVLP. We also get a lot of enquiries from colleagues around the country and we can steer them in the right direction.
My colleague Dr Shivan Sivakumar is conducting a vaccine study for pancreatic cancer and I am pleased that QEHB is the first hospital in Europe to have opened the trial. We also have melanoma and lung cancer vaccine studies in our centre run by Dr Lalit Pallan and Professor Gary Middleton, respectively. It would be great to see these studies incorporated into the CVLP. Other hospitals around the country are conducting similar studies in various tumour sites. CVLP is about improving access and delivering the studies to patients with the aim of improving patient outcomes.
What are your hopes for the future of the colorectal cancer vaccine trial, the CVLP as a whole and their impact on patients?
When patients hear about CVLP and start to understand the science behind the personalised vaccine, the uptake is relatively high. People want to improve their chances of survival as much as possible, but they also want to take part for the benefit of others. Most of them say: ‘I just want to contribute to the future’.
All these patients have shown a lot of selflessness, saying, ‘even if it doesn’t help me, if it helps somebody else, I’ll be happy to take part in it’. And that’s amazing.
I know there’s a lot of criticism of the NHS and that things could be better in certain areas. I agree. However, some aspects of NHS are beyond the ability of one person or Trust to deliver and we need that coordinated effort to provide something as big as this.
The United Kingdom is doing very well and recruiting faster than other countries. We are really proud of what we are doing. We should build on this model to deliver other research that will only benefit patients.
Dr Victoria Kunene, consultant medical oncologist at Queen Elizabeth Hospital Birmingham, UK, was speaking to pharmacist and medical writer Steve Titmarsh.
