Australian first: On-site vector production and use in gene therapy trial

Australian first: On-site vector production and use in gene therapy trial

Break-through research has reached an exciting stage of maturity.  

Donors to The Kids’ Cancer Project can be proud of their investment in break-through research that has reached an exciting stage of maturity.

For eight years, The Kids’ Cancer Project has been funding the ground-breaking work of Drs Belinda Kramer and Geoffrey McCowage at Kids Research, the dedicated translational research centre for The Children’s Hospital at Westmead.

Owen Finegan, the charity’s CEO is proud to have supported the deductive duo in their gene therapy and CAR T cell work.

"Since 2010, we have been able to commit $3,900,000 toward this project,” Mr Finegan said. “Our organisation’s early commitment has allowed the team at The Children’s Hospital at Westmead to scale up therapies including the initiation of a clinical trial for childhood cancer patients."

The research, initiated nearly twenty years ago by Dr McCowage, a paediatric oncologist, was a collaborative effort from clinicians and research teams at the Children’s Cancer Research Unit (CCRU) and the Gene Therapy Research Unit (GTRU).

Now, results of a Phase I Clinical Trial which employed genetic engineering technologies developed on-site at Kids Research have been published in Human Gene Therapy. It is the first example of a group in Australia to succeed in safely manufacturing and using clinical-grade vectors.

Dr Belinda Kramer of CCRU, together with Professor Ian Alexander of GTRU, led the design and development of the trial vector and protocol.

Gene therapy is a technology that involves introducing a new or repaired version of a gene into the body. Once cells have been removed from the body, this can be done using a viral vector, which shuttles the desired gene into the cell’s DNA. The cells can then be reintroduced into the patient.

In this study, a transport vector was used to insert a gene encoding methyl-guanine methyl transferase (MGMT), a naturally-occurring protein that protects cells against the effects of various chemotherapeutic agents, into the bone marrow cells of children undergoing chemotherapy.

Normally, vectors are commercially sourced from overseas at great financial cost. In an Australian first, this study built the capacity to make clinical-grade vectors on-site, using specialised cleanroom infrastructure provided by the Gene and Cell Medicine Facility at Kids Research.

The challenge in making and using vectors lies not only in the complex manufacturing process, but in satisfying the rigorous regulatory process for approval for use in a clinical trial. The regulatory experience gained from this study is invaluable, and has set a foundation that will underpin future gene and cell therapy trials at Sydney Children’s Hospitals Network.

At the conclusion of the trial, although positive results had been reported in the adult patient group, results were not as anticipated for the paediatric patients. Unfortunately, although bone marrow cells incorporated the introduced gene, it was difficult to obtain sustained engraftment of these cells to a level that could have led to a reduction in the side effects of treatment and to allow for dose escalation of chemotherapy.

Despite this result, the project has had other positive outcomes. In establishing the capacity to develop vectors for gene therapy on site at The Children’s Hospital at Westmead, researchers and clinicians can react to the needs of patients more efficiently and at a substantially lower cost than if the vectors were commercially sourced. This has facilitated the accelerated translation of innovative research from bench to bedside, and in therapeutic applications beyond cancer.

Valuable experience gained in the conduct of the trial is now being used to inform and advance a new immunotherapy program for paediatric cancer patients with solid tumours who have relapsed after initial treatment.

Using the Gene and Cell Medicine Facility and their significant expertise in the field, Dr Kramer’s team at the CCRU is now developing a new vector to be used to genetically modify T cells. This would allow them to identify, bind to and kill solid tumour cells.

Mr Finegan is excited by this next phase of the study.

"Continued funding from The Kids’ Cancer Project has allowed translation of these scientific discoveries into yet another early phase clinical trial,” Mr Finegan said.

"Our donors can take pride in knowing they’ve played a role in making therapies available to patients at an earlier stage of treatment, rather than as an experimental option following treatment failure."

In more good news for families affected by childhood cancer, research into gene therapy will now be supported through grants issued by the NSW Government. Information released by the Office of Health and Medical Research states that the grants aim to position the State as a global leader, supporting projects to reduce the time between gathering evidence of effective treatments to delivering those treatments at scale; deliver innovative therapies rapidly, efficiently and effectively; and engage commercial and industry partners early to rapidly scale up therapies found to be effective.


"It is exciting to hear the Office of Health and Medical Research have launched NSW Health’s Cell and Gene Therapy Grants,” said Mr Finegan. “We look forward to NSW becoming a leader in the development, delivery and commercialisation of innovative cell and gene therapies."

Dr Kramer looks forward to a successful bid for a slice of the funding on offer through the Gene Therapy Grants.

"We are very excited about the prospect of funding being available through the Office of Health and Medical Research,” said Dr Kramer. “This represents a great opportunity to translate our pre-clinical work into a clinical trial more quickly, and also supports cell and gene therapy activity within NSW to further consolidate efforts and make faster progress into the clinic for our patients."

"We wouldn’t be in a position to be involved in this proposal without The Kids’ Cancer Project’s long-term investment in our work,” she said.