The funded projects will be investigating why some lung cancer patients are resistant to a particular immunotherapy, how women's cancers become resistant to treatment, how to improve CAR T-cell therapy for patients with aggressive lymphoma, and how to engineer CAR T-cells to make them work better against solid tumours.

Funded by the Victorian Government, the VCA invests in projects that rapidly translate research into treatments and approaches that improve clinical practice and care of cancer patients.

Below are summaries of the research projects:

• Dr Fiona Hegi-Johnson – Defining the immunophenotype of durvalumab resistance with durvalumab and T-cell PET/CT (Early Career Research Fellowship)

This project aims to see if palliative radiotherapy can improve the immunotherapy sensitivity of lung cancers, and to understand why they become resistant, using two new PET tracers that show if cancer cells take up durvalumab, an immunotherapy that improves survival in lung cancer, and shows where the cancer-killing T-cells are located. It will see if palliative radiotherapy can make immunotherapy work better by increasing the infiltration of T-cells and explore why immunotherapy resistance develops. This study will identify why patients respond to immunotherapy using technology that is non-invasive and allows assessment at multiple time points in a patient's cancer treatment, resulting in safer and more effective immunotherapy treatment.

• Dr Liz Christie – Investigating treatment response in women's cancers (Mid-Career Research Fellowship)

This projects aims to generate new knowledge of the treatment resistance mechanisms that arise in women with ovarian and endometrial cancer, and identify effective treatments to overcome resistance. Part one of the program involves examining the evolution of tumours to discover resistance mechanisms, and part two involves translational studies to identify treatments and biomarkers. This study is designed to address current gaps in knowledge so that findings can be rapidly translated into the clinic, transforming the clinical management of women's cancers and improve survival outcomes.

• Dr Mark Dowling – Adding other drugs to improve the efficacy, durability and cost effectiveness of CAR T-cell therapy for aggressive lymphoma (Mid-Career Research Fellowship)

Chimeric Antigen Receptor (CAR) T-cell therapy is an exciting new treatment for patients with blood cancers that uses a patient's own immune cells to attack and destroy cancer. Some patients are cured who previously would have had no good treatment options, however these are in the minority. This clinical trial will test a range of possible additional drugs that are given before, during or after CAR T-cell therapy with the aim of increasing the long-term cure rate of CAR T therapy. Patient samples will be used to better understand the immune response that results in a cure.

• Dr Ian Parish – Engineering exhaustion-resistant CAR T-cells to treat solid tumours (Mid-Career Research Fellowship)

CAR T-cell therapy is where a patients' own immune cells are genetically engineered to attack and kill cancer cells. While this therapy works well against blood cancers, it is less effective against solid tumours because of a process called 'exhaustion' that suppresses the CAR T-cell response against the cancer. This research proposal will use cutting-edge genetic engineering to manufacture 'exhaustion-resistant' CAR T-cells to better treat a range of solid tumours, such as breast, lung, ovarian and colon cancer.

The VCA also acknowledged the strength of Dr Pilar Dominguez's application for her project entitled 'Optimising epigenetic therapies in blood cancers', but did not award her funding as she previously received a NHMRC Ideas grants in 2021.

For more information, or to arrange an interview with a VCA Fellowship recipient, contact the Peter Mac Communications team on 0417 123 048.

Photo: Killer T-cells surround a cancer cell. Credit: Alex Ritter, Jennifer Lippincott Schwartz & Gillian Griffiths, National Institutes of Health

The award was presented at the NHMRC Research Excellence Awards ceremony held in Canberra overnight.

The TOPGEAR Phase III clinical trial is trying to answer one of the most important questions in gastrointestinal oncology.

"We want to determine what is the best combination of chemotherapy, radiotherapy and surgery to improve cure rates for patients with gastric cancer," Professor Leong says.

"And clinicians across the world are eagerly awaiting our results."

Gastric cancer – which occurs when cancerous cells form in the lining of the stomach – is the second most common cause of cancer-related death globally.

In Australia, 2,000 people are diagnosed with gastric cancer each year. Worldwide it's estimated to be one million people diagnosed annually.

For decades, surgery was the only option available to cure patients with operable gastric cancer. However, five-year survival rates following surgery alone were dismal.

In the early 2000s, chemotherapy and radiotherapy were added to surgery, improving patient cure rates.

Currently, there are two global standards of care for patients undergoing surgery for gastric cancer: one that uses chemotherapy alone, and one that uses both chemotherapy and radiotherapy.

But oncologists are divided as to which approach is the most effective – hence the significance of a large randomised clinical trial like TOPGEAR.

Led by the Australasian Gastro-Intestinal Trials Group (AGITG), of which Professor Leong is a Director, TOPGEAR began recruiting patients in Australia in 2009 before opening to international patients in 2013.

It reached its target of 570 patients successfully enrolled in May 2021.

The trial has established over 70 sites in Europe, North America, New Zealand and Australia in 15 different countries, including collaborations with the European Organisation for Research and Treatment of Cancer (EORTC) and the Canadian Cancer Trials Group.

"These collaborations have propelled TOPGEAR to international recognition and will allow this Australian-led trial to set the standard of care and improve treatment outcomes globally," Professor Leong says.

"Even before the trial results become available, TOPGEAR has already provided benefits for patients with gastric cancer by fostering multidisciplinary management, and raising standards for the delivery of surgery and radiation therapy."

The latest NHMRC grant TOPGEAR received is the third the trial has been awarded, and reflects that it is truly interdisciplinary and international and its outcomes will be of global significance, says Professor Leong.

The NHMRC David Cooper Clinical Trials and Cohort Studies Award – previously the NHMRC Clinical Trials and Cohort Studies Award – has been renamed to honour the achievements of the late Australian HIV/AIDS clinical research Professor David Cooper AC.

This award recognises Professor Leong as the highest ranked recipient in the Clinical Trials and Cohort Studies Grant scheme.