Scientists present a finding – published in the journal Cancer Research- that an antibody against the protein EphA3 has antitumor effects, providing a new approach to treat solid tumors.
As EphA3 is present in normal organs only during embryonic development but is expressed in solid tumors, this antibody-based approach may be a suitable candidate treatment for solid tumors.
Tumor cells, without EphA3 in itself, can thrive by recruiting and taking advantage of supporting EphA3-containing cells in the tumor microenvironment.
As we know, the tumor cells send out signals to the surrounding area, seeking a blood supply and a foundation upon which to spread. And EphA3-expressing stromal stem cells, once receiving signals, can form cells that support and create blood vessels in tumors.
In the experiment where human prostate cancer cells were introduced into a mouse model, researchers found EphA3 in stromal cells and blood vessels surrounding the tumor.
Also, they observed the treatment with an antibody against EphA3 (chIIIA4) significantly slowed tumor growth. The antibody damaged tumor blood vessels and disrupted the stromal micro-environment, and cancer cells died because their ‘life-support’ was compromised.
The microenvironment is so important for tumor cell survival that monoclonal antibodies against EphA3 can act as one way to kill a variety of solid tumors by disrupting their microenvironment.
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.
Targeting EphA3 Inhibits Cancer Growth by Disrupting the Tumor Stromal Microenvironment. Cancer Research, 2014; 74 (16): 4470