New ways to treat solid tumours

New ways to treat solid tumours

(Medical Xpress)—An international team of scientists has shown that an antibody against the protein EphA3, found in the micro-environment of solid cancers, has anti-tumour effects. 

As EphA3 is present in normal organs only during embryonic development but is expressed in 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 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 in tumours," Dr Vail said. 

Professor Andrew Scott's team at Ludwig introduced human 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 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 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.

More information: Cancer Researchcancerres.aacrjournals.org/content/74/16/4470.full

add to favorites email to friend print save as pdf

Related Stories

Life work culminates in testing of cancer therapy in humans

Mar 24, 2011

A cancer-fighting antibody identified by a researcher working at The University of Queensland and Queensland Institute of Medical Research (QIMR) will today be used to treat the first patient, in a Phase 1 clinical trial.

Brain tumour cells found circulating in blood

Aug 01, 2014

(Medical Xpress)—German scientists have discovered rogue brain tumour cells in patient blood samples, challenging the idea that this type of cancer doesn't generally spread beyond the brain.

New drug candidate starves dormant cancer cells

Feb 18, 2014

In a study published in Nature Communications, researchers at Karolinska Institutet and Uppsala University in Sweden present a new drug candidate, which selectively kills dormant cells within a cancer tumour through starva ...

Recommended for you

The fine line between breast cancer and normal tissues

15 hours ago

Up to 40 percent of patients undergoing breast cancer surgery require additional operations because surgeons may fail to remove all the cancerous tissue in the initial operation. However, researchers at Brigham ...

Pancreatic cancer risk not higher with diabetes Rx DPP-4i

16 hours ago

(HealthDay)—There is no increased short-term pancreatic cancer risk with dipeptidyl-peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) and thiazolidinediones (TZD) for glycemic control, according ...

Good bowel cleansing is key for high-quality colonoscopy

18 hours ago

The success of a colonoscopy is closely linked to good bowel preparation, with poor bowel prep often resulting in missed precancerous lesions, according to new consensus guidelines released by the U.S. Multi-Society Task ...

User comments