When Professor Jordan Hansford sits down with the parents of a child whose brain tumour has come back, the conversation has rarely changed in twenty years. Standard chemotherapy has run out of options. Re-irradiation may buy weeks, sometimes months. For the most aggressive paediatric brain cancers, particularly diffuse midline glioma, the median overall survival is still roughly nine to twelve months from diagnosis. Now, for the first time, Hansford, the clinical lead of PaedNEO-VAX based at SAHMRI and Adelaide University, can offer families something genuinely new: a vaccine designed from scratch, in roughly ten weeks, around the unique genetics of their child's own tumour.
A world-first trial, by design
PaedNEO-VAX is the first multi-site paediatric trial anywhere in the world of personalised mRNA neoantigen vaccines for children and adolescents with brain cancer. It is co-led by the University of Queensland's Frazer Institute, where Professor Brandon Wainwright heads the scientific programme, and by SAHMRI, where Hansford directs the clinical effort. The trial is sponsored by the Australia and New Zealand Children's Haematology and Oncology Group (ANZCHOG), and supported by Providence Therapeutics, a Calgary-based clinical-stage mRNA biotechnology company whose proprietary lipid nanoparticle delivery platform underpins the vaccine construct [1][2][3][4].
Up to around 70 children and adolescents, aged approximately 5 to 21, will be enrolled across eight Australian paediatric oncology centres in Queensland, South Australia, New South Wales, Victoria and Western Australia, with recruitment opening progressively from 2026 over a planned four-year window [1][2][6]. Children and young people with relapsed or refractory high-grade brain tumours, including medulloblastoma, ependymoma and high-grade glioma, are eligible; the conference programme for the mRNA-Based Therapeutics Summit indicates that newly diagnosed diffuse midline glioma (DMG) may be included as a separate sub-cohort, a detail to confirm directly with the trial sponsor [1][2][3][7].
The federal contribution is approximately AUD $2.578 million from the Medical Research Future Fund, supplemented by Providence Therapeutics and philanthropic donors [1][3][4][5]. A small discrepancy in the source materials deserves flagging: Providence's press release cites seven participating hospitals, while Australian sources cite eight. The most likely explanation is that one site is opening in a second wave rather than day one [1][2][3][4][5][6]. Families seeking the official record on federal funding and site activation should contact ANZCHOG directly.
The science, in plain language
A neoantigen is a small protein fragment on the surface of a cancer cell that arises from a mutation unique to that tumour. Because the immune system has never encountered these fragments during early development, they look foreign, and T cells can in principle be trained to recognise and kill any cell displaying them. A personalised mRNA vaccine delivers genetic instructions, wrapped in a lipid nanoparticle, that tell the patient's own cells to manufacture a curated set of these neoantigens, training the immune system to seek out residual cancer cells that survived surgery, chemotherapy or radiation [8][9].
After enrolment, a child's tumour and a matched normal sample, usually blood, undergo whole-genome sequencing. Bioinformaticians compare the two to identify neoantigens predicted to bind strongly to that patient's own tissue-type, or HLA, molecules. A bespoke mRNA construct encoding a curated panel of such neoantigens is then manufactured by Southern RNA in Australia, with a target turnaround of approximately ten weeks from enrolment to first dose [1][4][5]. The vaccine is given as a series of intramuscular injections, typically alongside an immune checkpoint inhibitor, and the immune response is monitored in the blood over time.
This is meaningfully different from a conventional cancer vaccine in three ways. The construct is individual: no two children receive the same vaccine. The antigenic targets are tumour-specific mutations rather than shared tumour-associated proteins, which reduces the risk that the immune response attacks healthy tissue. On the platform side, once the bioinformatics and manufacturing workflows are in place, the same process can be turned around for any patient whose tumour can be sequenced [8][9]. That scalability is part of what makes this class of therapy a credible candidate for the rare and heterogeneous mix of paediatric brain tumour types.
What the adult trials have, and have not, shown
PaedNEO-VAX is a first-in-paediatric study, so it draws its scientific justification almost entirely from adult trials in melanoma and pancreatic cancer. Two studies in particular have shaped the field.
In a first-in-human Phase I trial published in Nature in 2023, Rojas and colleagues administered an mRNA neoantigen vaccine called autogene cevumeran (BNT122) alongside the checkpoint inhibitor atezolizumab and standard chemotherapy to 16 patients with resected pancreatic ductal adenocarcinoma, one of the most treatment-resistant cancers in adults. Half of the patients (8 of 16) mounted a de novo, high-magnitude CD8+ T cell response that was not detectable before vaccination, and vaccine-expanded T cells were still detectable in some patients up to three years after surgery. Patients who mounted a response had a markedly longer median recurrence-free survival than non-responders, providing proof-of-concept that a personalised mRNA neoantigen vaccine can drive clinically meaningful anti-tumour immunity even in a typically "cold" cancer [8].
In melanoma, the evidence is more mature. The KEYNOTE-942 / mRNA-4157-P201 study, a randomised Phase 2b trial published in The Lancet in 2024, enrolled 157 patients with resected high-risk stage III or IV melanoma and randomised them to receive either pembrolizumab alone, or pembrolizumab plus a personalised mRNA-4157 vaccine (now known by the generic name intismeran autogene). At a median 23 months of follow-up, the combination reduced the risk of recurrence or death by 49% (HR 0.51, 95% CI 0.31 to 0.83) and the risk of distant metastasis or death by 62% (HR 0.38), with a similar safety profile to pembrolizumab alone [9]. Updated analyses at roughly 34 months, and now at five years (presented at ASCO 2025), have shown that the recurrence-free and distant metastasis-free survival benefit is durable, supporting the ongoing Phase 3 INTerpath-001 study [10][11].
These results are encouraging signals, not a licence to expect similar benefit in children with brain cancer. Paediatric brain tumours differ from adult melanoma and pancreatic cancer in tumour biology, in the integrity of the blood-brain barrier, and in the developing immune system of the host. Phase I/II trials of this size, with a primary endpoint of safety and a secondary endpoint of disease response, are designed to find a signal, not to deliver a cure.
The Australian foundation: ZERO and PRISM
PaedNEO-VAX does not arrive in a vacuum. It builds on more than a decade of national paediatric precision-medicine infrastructure in Australia, principally the Zero Childhood Cancer (ZERO) program, led by the Children's Cancer Institute and the Kids Cancer Centre at Sydney Children's Hospital, Randwick [14].
The PRISM study, published in Nature Medicine in 2024, enrolled 384 Australian children with high-risk cancer and a predicted survival below 30%. Each child underwent whole-genome, transcriptome and DNA methylation analysis, with results returned to a national molecular tumour board. Patients who received a precision-guided therapy had a two-year progression-free survival of 26% and overall survival of 38%, compared with 12% and 24% respectively for those who did not. Fifty-five per cent showed clinical benefit, and a third had an objective response. When all three of the strongest predictors were present (high-quality molecular data, a structural variant such as a fusion gene, and early treatment), two-year progression-free survival reached 88% [12][13].
The relevance for PaedNEO-VAX is twofold. It shows that the bioinformatics and rapid-turnaround molecular profiling needed to design a personalised therapy already exists, at scale, in Australian paediatric oncology. It also shows that children with relapsed and refractory brain tumours are precisely the group in whom conventional therapy has the most to gain, and the most to lose, from any new intervention. Associate Professor Vanessa Tyrrell reported at the 2024 European Human Genetics Conference that more than 1,600 children have been enrolled in ZERO since 2017, and that ZERO2, the national roll-out, is now open at all Australian paediatric oncology centres, with New Zealand to follow [13].
"Our study provides important new evidence that response to precision-guided therapy translates into improved survival. This work provides some hope to families where none previously existed in a new model of treatment for high-risk childhood cancer which is changing national and international clinical practice."
That statement, from PRISM co-authors Dr Loretta Lau and Professor Glenn Marshall, captures the careful tone that paediatric oncologists are trying to strike with families in 2026: hope grounded in data, not in promise [12].
What families should know, and not assume
Brain cancer remains the leading disease-related killer of Australian children and the most common solid tumour diagnosed in this age group. Approximately 120 children are diagnosed with brain cancer in Australia each year, across roughly 100 distinct subtypes, and overall five-year survival is approximately 23% [15][16][17]. For some subtypes, such as medulloblastoma, five-year survival is now around 70% on standard therapy; for ependymoma, outcomes depend heavily on whether a gross total surgical resection can be achieved [17][18][19]. For diffuse intrinsic pontine glioma (DIPG), the most common diffuse midline glioma, it is approximately 2% [15][17][18][20].
For families whose child has been diagnosed with a relapsed or refractory medulloblastoma, ependymoma, high-grade glioma, or, potentially, a newly diagnosed diffuse midline glioma, the practical pathway into PaedNEO-VAX runs through the treating paediatric oncologist at one of the participating tertiary centres. As of mid-2026, the trial is in the process of opening, not yet enrolling publicly; the most reliable first step is a conversation with the child's oncologist, who can refer the family to the nearest site team, and through them to ANZCHOG.
A few points are worth being explicit about. This is a Phase I/II trial, with a primary goal of establishing safety and identifying the optimal dose; the number of children who can expect clinical benefit is genuinely unknown, and the trial is not designed to deliver, nor should it be promoted as delivering, a cure. Manufacturing takes around ten weeks from enrolment to first dose, a window during which a child's disease can progress, and eligibility is restricted to specific tumour types. The pancreatic and melanoma data are the strongest evidence available that personalised mRNA neoantigen vaccines can work in cancer at all, and they are evidence in adults, not children, and in cancers that are biologically very different from paediatric brain tumours.
The honesty of the field, in this trial and others like it, is to put that uncertainty on the table, and to keep going. Adam Sorenson, the teenage son of Providence Therapeutics' founder Brad Sorenson, was diagnosed with glioblastoma multiforme (GBM) in 2013 and given roughly twelve months to live. In early 2024 the cancer recurred, and Adam became the first person to receive a Providence personalised cancer vaccine outside a clinical trial.
"In early 2024 that horrible day came when his GBM recurred in his brainstem and throughout his spine, and we rushed to make a personalized vaccine for him. Adam was the first person to receive a Providence cancer vaccine, and he responded remarkably well. It is a rare good-news story, and he is still doing well today."
That is Brad Sorenson's account, in Providence Therapeutics' press materials, of his own son's treatment [4]. It is, as the press release itself notes, one case, and a parent's account at that. The vehicle now bringing the technology to Australian children is PaedNEO-VAX itself.