Immunotherapy for mesothelioma: Potential drugs or pipe dreams?Because malignant pleural mesothelioma (MPM) is such a recalcitrant disease, one that does not always yield to typical therapies, researchers are all too happy to make MPM the target of experimental treatments. For this reason, scientists have adopted a number of novel therapeutic modes to treat mesothelioma, from gene therapy and light-activated chemo to the budding field of immunotherapy.
The latter method is the subject of a review newly published by the journal Lancet Oncology. In the report, molecular biologists from the National Cancer Institute (NCI) discussed the ups and downs of using the immune system to attack MPM, noting that this system is promising, if tricky to deploy.
Coley's toxins yield key insight
While it might seem like a relatively new form of cancer treatment, immunotherapy is more than a century old. It began in the late 1880s, when a New York oncologist bone surgeon named William Coley noticed something unusual while going through patient records.
He found that a man named Fred Stein, who'd been diagnosed with a bone sarcoma, had fallen ill with erysipelas, a severe strep infection. Later, when examining Stein, his doctors noted that the tumor seemed to have vanished, for no reason they could see.
However, Coley thought he knew the reason. He suspected, based on similar cases, that bacteria like Streptococcus pyogenes (the strain that causes erysipelas) and Serratia marcescens were causing people's immune systems to attack tumors.
To test his theory, he vaccinated cancer patients with a mixture of dead S. pyogenes and S. marcescens, a cocktail later nicknamed "Coley's toxins." To an extent, it worked, with some individuals going into remission.
Immunotherapy was born.
Active immunotherapy attacks tumor cells
In the new review, the NCI-based authors described a number of different immunotherapies that might have an effect on MPM growth. These included:
- Listeria-based vaccines. In this method, live Listeria bacteria are loaded with MPM-specific antigens. When injected into the blood, these microbes tag tumors with the antigens, which tell the immune system to attack.
- WT1 analogue peptide vaccines. In certain kinds of mesothelioma, the tumors emit high levels of the protein WTI. This form of immunotherapy directs the white blood cells to attack areas of the highest WTI concentration.
- Dendritic cell immunotherapy. In this relatively new form of treatment, doctors harvest dendritic cells (the immune system's messenger cells) and modify them to antagonize MPM tumors. The cells are then reinjected into the bloodstream.
In the review, researchers noted that while immunotherapy is quite promising, it is also tricky to apply, since mesothelioma cells mutate and grow very fast.
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