New Ways to Treat Solid Tumours
News Aug 15, 2014
As EphA3 is present in normal organs only during embryonic development but is expressed in blood cancers and in solid tumours, this antibody-based approach may be a suitable candidate treatment for solid tumours.
The researchers from Monash University and Ludwig Cancer Research, in Australia, and KaloBios Pharmaceuticals, in the US, have had their findings published in the journal Cancer Research.
The team, led jointly by the late Professor Martin Lackmann, from the School of Biomedical Sciences at Monash; and Professor Andrew Scott, from Ludwig Cancer Research, has found that even if tumour cells do not have this molecule they can thrive by recruiting and taking advantage of supporting EphA3-containing cells in the tumour micro-environment.
First author, Dr Mary Vail, Monash Department of Biochemistry and Molecular Biology said: “The tumour cells send out signals to the surrounding area and say: ‘We need a blood supply and a foundation upon which to spread’.”
“We have shown that EphA3 expressing stromal stem cells, which are produced by the bone marrow, form cells that support and create blood vessels in tumours,” Dr Vail said.
Professor Andrew Scott’s team at Ludwig introduced human prostate cancer cells into a mouse model to mimic disease progression in humans. EphA3 was found in stromal cells and blood vessels surrounding the tumour.
They also observed that treatment with an antibody against EphA3 (chIIIA4) significantly slowed tumour growth. The antibody damaged tumour blood vessels and disrupted the stromal micro-environment, and cancer cells died because their ‘life-support’ was compromised.
“In addition, we screened various tumours from patient biopsies - sarcomas, melanomas as well as prostate, colon, breast, brain and lung cancers - and confirmed EphA3 expression on stromal cells and newly forming blood vessels,” Professor Scott said.
“Our research findings indicate that the tumour micro-environment is important, and monoclonal antibodies against EphA3 are one way to target and kill a variety of solid tumours as well as blood cancers.”
Currently, KaloBios Pharmaceuticals is testing the anti-EphA3 antibody KB004 in a multi-centre Phase I/II clinical trial in Melbourne and the US in patients with EphA3 expressing blood malignancies: AML, MDS and myelofibrosis.
Dr Vail, who collaborated with her former mentor on the project for 10 years, said this research represented Martin Lackmann’s life work.
“Martin was dedicated to helping people, and believed that KB004 was a promising therapeutic approach. He rightly anticipated that it would be well-tolerated in cancer patients, and through this collaborative project, his pioneering research has progressed to clinical trials and potentially new treatments for cancer patients,” Dr Vail said.
The research study was funded by ARC, NHMRC and KaloBios Pharmaceuticals.
Insulin Goes Viral: Diabetes and Cancer-causing Mechanisms ExploredNews
Every cell in your body responds to the hormone insulin, and if that process starts to fail, you get diabetes. In an unexpected finding, scientists have identified four viruses that can produce insulin-like hormones that are active on human cells. The discovery brings new possibilities for revealing biological mechanisms that may cause diabetes or cancer.READ MORE
Pre-Clinical Safety in Cancer Drug Development: “Attitude to Safety Needs to Change”News
Many companies involved in cancer drug research and development need to re-think their use of safety data in helping to bring new drugs to cancer patients.
Dr Richard Knight of ApconiX will tell this month’s conference, that greater focus on pre-clinical safety should be fundamental to the development of new cancer therapies.
Understanding the Process of Cell DivisionNews
Using multiple techniques such as structural modelling, X-ray scattering, X-ray crystallography and electron microscopy, scientists have found that the Spc110 protein provides a greater function in mitosis originally believed. This information could help understand the process in human cells and the abnormalities that occur in cancer.READ MORE
Comments | 0 ADD COMMENT
Next Gen Regenerative Medicine & Tissue Engineering
May 29 - May 30, 2018