UCLA researchers develop promising new combo treatment for deadly brain cancer

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A recent article, http://www.newswise.com/articles/ucla-researchers-develop-a-likely-new-combo-treatment-for-the-deadliest-form-of-brain-cancer,  by my colleague Dr. Robert Prins at UCLA  in the prestigious journal Neuro Oncology has drawn significant attention.  Dr. Prins works with Dr. Linda Liau at UCLA developing immunotherapy approaches for treating glioblastoma.  Immunotherapy for cancer is a rapidly evolving field.  To the lay person it can be quite confusing.  There are several key points that need to be understood about immunotherapy and cancer to understand Dr. Prins’ recent publication.

First, the goal of immunotherapy for cancer is to somehow focus the inherent immune response against a tumor.  This can be quite difficult because of two issues.  First, tumors are derived from your body’s own cells, and normally the immune system has not developed an ability to attack your own tissues.  Secondly, part of the process of tumor development often requires that the tumor cells produce factors that turn off the immune response.  Tumor cells do this by secreting molecules that are immunosuppressive, and by having cells of the immune system themselves become inactivated.  These tumor fighting cells, known as cytotoxic T cells, can become inactivated if they express markers called PD1 or CTL A4.  A big breakthrough recently in cancer immunotherapy has resulted from a new abiltiy to knock out these inactivating molecules on cytotoxic T cells by giving patients blocking antibodies drugs.  However these drugs that block the inhibitory molecules on cytotoxic T cells still do not tell year immune system how to specifically target a tumor.

If however you could design some strategy to cause tumor cells to express molecules at a much higher level in the tumor than the rest of the body, then you could target that molecule with an immune strategy and theoretically get selective tumor killing.  There is a molecule that is often expressed in cancers at a high level that goes by the name  NY-ESO-1, which is normally not expressed in glioblastoma cells.  Dr. Prins found that if you treat glioblastoma cells with a chemotherapy drug, it will make the tumor cells produce high levels of this protein marker NY-ESO-1.  That is step one–labeling the tumor cells with a specific marker to be targeted by the immune system.  The second step of the strategy is giving immune cells to the patient that target this specific marker NY-ESO-1.

Dr. Prins showed that glioblastoma cells implanted into mice that are treated with the chemotherapy will start producing high levels of NY-ESO-1.  If these mice are then given cytotoxic T cells that have been designed to attack the NY-ESO-1 marker, then the immune cells will kill the tumor cells.  There was no significant side effect in the mice treated with this strategy.

These findings raise the possibility that a two-step strategy such as this could be used in human glioblastoma patients.  If we could give glioblastoma patients a chemotherapy drug that caused their tumor cells to selectively produce high levels of a marker that the immune system could attack, then this strategy might lead to a specific targeting approach for glioblastoma.  It might be possible to design specific cytotoxic T cells to give to these patients that target this NY-ESO-1 protein, and lead to specific tumor cell killing.

Before such a strategy can be used in humans, it will be necessary to determine if step one of this process actually does induce this specific protein in human glioblastoma patients tumors in the patient’s themselves.  The implications are exciting and hopefully this work will lead to specific targeting of an immunotherapy approach for glioblastoma.

 

 

 

 

 

 

 

 

 

 

 

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