ºÚÁϳԹÏȺÍø

Immunotherapy is the rich new frontier revolutionising cancer treatment - harnessing the natural powers of the immune system to fight disease, writes Professor Mark Smyth, Ìýhead of the Immunology in Cancer and Infection Laboratory at QIMR Berghofer Medical Research Institute.Ìý
The immune system’s unique properties offer great potential compared to current treatment regimens by:

• fighting cancer more powerfully;


• offering longer-term protection Ìýagainst the disease;


• causing few side effects; and


• offering treatment for more Ìý cancer types.

Immunotherapy is a fast emerging research area in the oncology divisions of major international pharmaceutical industries and academic centres of cancer medicine.
The QIMR Berghofer Centre for Immunotherapy and Vaccine Development includes more than 200 staff and students across 14 laboratories, focused on mobilising the immune system to fight cancer and develop new vaccine strategies.
Substantial progress is being made with several types of immunotherapies, including antibodies that block immune checkpoint molecules, adoptive cellular therapies, and cancer vaccines.
The Immunology and Infection laboratory at QIMR Berghofer has used pre-clinical models to define many of the founding principles of the immune reaction with cancer, including immune-mediated tumour dormancy, or when the immune system supresses, but does not eliminate, cancer cells.
More recently we have described a new immune checkpoint molecule on immune cells produced within the bone marrow.
Cancers co-opt certain immune checkpoint pathways as a major mechanism of immune resistance, particularly against T-cells that specifically target antigens created by natural cancer mutations.
These immune checkpoints can be readily blocked by monoclonal antibodies.
There have been impressive results of late in many cancer types, such as melanoma, non-small cell lung cancer, renal cancer, and bladder cancer.
An even better response rate - 53 per cent overall - in melanoma patients treated with a combination of antibodies, highlights the need to study immunotherapy cocktails to bring the power of this approach to more patients.
A colleague at QIMR Berghofer, Professor Rajiv Khanna, is successfully translating his research on cellular immunotherapies to develop immunebased therapeutic strategies for the treatment of cancer patients.
Professor Khanna has made a major breakthrough in the treatment of the aggressive brain cancer Glioblastoma Multiforme (GBM).
In Phase I clinical trials - conducted in collaboration with Dr David Walker at Brisbane’s Wesley ºÚÁϳԹÏȺÍø - most participants lived much longer than the sixmonth prognosis normally given to a patient with recurrent GBM, and some patients showed no signs of disease progression.
This study built on previous research which found that many brain tumours carry cytomegalovirus (CMV).
Professor Khanna developed a technique to modify the patients’ T-cells in the laboratory, effectively train them to attack the virus, and then return them to the patient’s body.
When the killer T-cells destroyed the virus, they also destroyed the cancer.
Professor Khanna has successfully used similar technology to target nasopharyngeal carcinoma (NPC) – an aggressive throat cancer prevalent in South East Asia.
A common herpes virus, Epstein-Barr virus (EBV) is present in the NPC cells – providing the immunotherapy target.
In a Phase I clinical trial for NPC, overall survival rates for immunotherapy patients was 523 days, compared to only 220 days in patients who did not receive the treatment.
This Phase I clinical trial was conducted in collaboration with Queen Mary ºÚÁϳԹÏȺÍø in Hong Kong.
Professor Khanna also demonstrated the treatment was safe, with only a few mild side-effects. Professor Khanna’s group is also collaborating with various clinical centres in Australia to develop adoptive immunotherapy for HodgkinÌýlymphoma and other B-cell lymphomas which are associated with EBV.
Professor Khanna’s immunotherapy program is funded under a major Flagship Research Program on Cancer Immunotherapy which is supported through the Rio Tinto Ride to Conquer Cancer. Under this program, Professor Khanna and his colleagues are also developing a special immunotherapy bank which will be able to provide Ìýoff-the-shelf cellular therapies for cancer patients.
There is a great opportunity for medical oncologists in Australia and abroad to participate in this growth area at QIMR Berghofer and more generally in the city of Brisbane.
While great research training opportunities exist in this area, the recruitment of a leading medical oncologist specialist in immunotherapy is a priority for the Institute to further translate its research and coordinate with national efforts in immunoncology in Australia and overseas.

Professor Mark Smyth

Professor Mark Smyth is a Senior Scientist at QIMR Berghofer Medical Research Institute, an NHMRC Australia Fellow, and Head of the Immunology in Cancer and Infection Laboratory. He completed his PhD in 1988 and trained at the NCI (19881992), before commencing his independent research career in Australia. In the previous 13 years at the Peter MacCallum Cancer Centre he rekindled world-wide interest in cancer immune surveillance, defined immune-mediated dormancy of cancer, and the role of the host in chemotherapy responses in mice and humans. More recently, Professor Smyth has provided new means of classifying natural killer cell (NK) subtypes and two new targets for cancer immunotherapy.

---

Ìý

QIMR Berghofer Takes ÌýMulti-pronged Approach to Cancer Research

Every day at QIMR Berghofer Medical Research Institute, hundreds of scientists are working on the next generation of treatments and diagnostic tools for more than a dozen deadly cancers.
This world-class research facility based at Herston in Brisbane, is helping to improve survival rates and life expectancy for cancer patients. Fifty per cent of all research undertaken at QIMR Berghofer relates to cancer, and half of its laboratories are dedicated to it.
The Institute’s scientists are investigating the genetics of cancer, how environmental factors such as sun exposure can cause or contribute to disease, and potential new treatments. These are Ìýas varied as arming the body’s own defences to fight cancer cells, to finding possible drugs already synthesised by nature.
As early detection is crucial, QIMR Berghofer scientists are also investigating more effective ways to diagnose a variety Ìýof cancers, to give those affected by the disease the best chance of survival.
The Institute owns Q-Pharm, Queensland’s leading early phase clinical trial facility, perfectly positioning it to translate important scientific discoveries into medicine. QIMR Berghofer is a non-profit organisation relying on funding from the Queensland Government along with research grants and fundraising to allow its crucial work to continue.
At QIMR Berghofer Medical Research Institute Ìýresearch is undertaken on:Ìý

• Blood cancers (including leukaemia, lymphoma and myelomas)


• Bowel (colorectal) cancer


• Brain cancer (glioblastoma)


• Breast cancer


• Endometrial cancer


• Lung cancer


• Melanoma


• Nasopharyngeal carcinoma (nose and throat cancer)


• Non-melanoma skin cancer (actinic solar keratosis, squamous cell carcinoma, basal cell carcinoma)


• Oesophageal cancer (including Barrett’s oesophagus)


• Ovarian cancer


• Pancreatic cancer

Ìý