Therapeutic potential of anti-PIGF for cancer and eye disease

Antibodies against PIGF protein can inhibit the growth of certain skin and liver tumors. This was demonstrated in a study by scientists in Leuven. Anti-PIGF can also inhibit the proliferation of blood vessels in the eye, the chief cause of age-related blindness.

Angiogenic switch
Our blood vessels supply all our tissues with oxygen and nutrients. Tumor cells grow and divide so rapidly that they require more oxygen and nutrients than other cells. This explains why tumor cells at a given moment start to produce massive amounts of growth factors to stimulate the development of blood vessels (angiogenesis). This step is known as the angiogenic switch. However, the resulting blood vessels have an abnormal shape, impeding the blood flow and thus the supply of oxygen to cancer cells. No sooner has the oxygen level dropped below a critical threshold, or growth factors such as vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) are produced to stimulate the development of blood vessels.

Anti-angiogenic cancer therapy
Anti-angiogenic cancer therapy is not new. It is the equivalent of starving the tumor. By inhibiting the development of blood vessels, the tumor cells are deprived of the necessary oxygen and nutrients. In 2007, Peter Carmeliet, VIB Vesalius Research Center, K.U.Leuven, published the first research results demonstrating the anticancer effect of anti-PlGF, an antibody against PlGF (Fisher et al., Cell, 2007). However, conventional anti-angiogenic cancer therapy involving elimination of the growth factor can speed up tumor metastasis. That is why in recent years more attention is being paid to anti-angiogenic therapies that normalize the blood vessels to the tumor, thus leading to improved oxygen supply, a reduction in the need for cancer cells to go searching for oxygen elsewhere in the body, and a more efficient delivery of anticancer drugs.

Anti-PlGF able to delay growth of skin and liver tumors
Recent work led by Peter Carmeliet and Massimiliano Mazzone, VIB Vesalius Research Center, K.U.Leuven, has gone a step further. They have demonstrated that PIGF also plays a role in spontaneous genetic and carcinogen-induced cancer models. The latter models are much more relevant to human pathology. The advantage is that PlGF is only found in pathological tissue, leaving angiogenesis in normal tissue unaffected. The researchers were able to show that in mice unable to produce PlGF or with their PlGF pharmaceutically blocked by anti-PlGF antibodies, the development of skin and liver tumors was delayed. This provides an important phenocopy for pharmacological and clinical studies.

Anti-PIGF can inhibit the proliferation of blood vessels in the eye.
Anti-PlGF was not only proven to stop the growth of tumor blood vessels but also to normalize them, thus preventing tumor metastasis and rendering the tumor less aggressive (Rolny C et al., Cancer Cell, 2011). (This mechanism was also described for PHD2 in a paper by Mazzone et al. in Cell, 2009.) It was also demonstrated that anti-PlGF inhibits abnormal blood vessel development in the eye, preventing age-related blindness (Van de Veire et al., Cell, 2010). Experiments in mice have shown that anti-PIGF reduces the development of abnormal blood vessels in the retina. It is an advantage that the drug does not have to be injected directly into the eye, as is presently the case for other blood vessel growth inhibitors, which are too toxic for systemic administration.

Van de Veire et al., ​Cell. 2010 Apr 2;141(1):178-90
Further Pharmacological and Genetic Evidence for the Efficacy of PlGF Inhibition in Cancer and Eye Disease.

tumor growth
© VIB, 2007