Some of the cancers such as lung and pancreatic cancer are known as epithelial cancers. This type of cancer uses the andalpha;andnu;andbeta;3 molecule to gain drug resistance to standard cancer therapies and to become highly metastatic. A recently published paper in Cancer Research, University of California San Diego School of Medicine confirms that the researchers identified a new therapeutic approach in mouse models that halts drug resistance and progression by using a monoclonal antibody that induces the immune system to seek and kill andalpha;andnu;andbeta;3-expressing cancer cells.
Cheresh and his team work on the andalpha;andnu;andbeta;3 antibody LM609 and observe the possibilities of its effect in cancer treatment. They exploited the appearance of andalpha;andnu;andbeta;3 receptors on tumor cells to redirect tumor-associated macrophages (TAMs) into recognizing and killing andalpha;andnu;andbeta;3 expressing tumor cells.
According to Cheresh, professor and vice chairman of the pathology, the developed antibody is designed to seek and destroy the most stem-like, drug-resistant, aggressive tumor cells. It does this by building a bridge between tumor-associated macrophages and these highly aggressive tumor cells.
Macrophages are the cells, which acts as a protective mechanism of the body. They are specialized immune cells that promote tissue inflammation, stimulate the immune system and rid the body of foreign debris, including cancer cells. Tumor associated macrophages performs an opposite fiction and creates pro-tumor environment that accelerates tumor growth, angiogenesis and suppresses immune recognition of the tumor by the host immune response.
The current study involves the modification of these Tumor associated macrophages in such a way that a reverse action is observed. This will result in the killing of cancer cells rather than supporting them. The mechanism of action of this antibody depends on the phenomenon of antibody-dependent cytotoxicity.
The protein CD47, which is found on many cells in the body and is often hijacked by cancer cells. This will send a signal to the macrophages and inform them about not to eat these cells. The andalpha;andnu;andbeta;3 antibody bypasses the CD47 preventive signal by inducing ADCC as opposed to phagocytosis. The team is currently producing a humanized version of this antibody and this will expected to perform the similar action as LM609 performs in mice.
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