Mesothelioma is an almost universally fatal cancer of the membranes that surround the lungs and line the abdomen. Conventional cancer therapies, including the chemotherapy regimen that has become the standard-of-care for mesothelioma, have done little to improve survival. Even after decades of research and the development of multi-modal treatments, most mesothelioma patients still die of the disease within a year of diagnosis.
But now, the outlook for this deadly cancer may finally be changing thanks to the emerging field of immunotherapy. Immunomodulators target the body’s own anti-tumor responses, effectively “turning them on” by blocking the processes (usually triggered by the tumor itself) that turned them off in the first place.
“The complexity of the immune system allows for many ways to therapeutically modulate anti-tumor immunity,” writes Mayo Clinic oncologist Aaron S. Mansfield, MD, in an online article for Contemporary Oncology.
Two new immunomodulators in particular have made news in recent months for their potential in the treatment of mesothelioma. Pembrolizumab, which is marketed under the brand name Keytruda and is FDA-approved to treat the most deadly form of skin cancer, is a monoclonal antibody that blocks a cell surface receptor called PD-1 (programmed cell death 1). University of Pennsylvania researchers recently reported an unprecedented 76 percent response rate in mesothelioma patients on pembrolizumab who had failed with other therapies.
PD-1 is one of two primary immune “checkpoints” that are the focus of much immunotherapy research for cancer. The second is cytotoxic T-lymphocyte antigen-4 (CTLA-4). This week, AstraZeneca, the makers of an anti-CTLA-4 monoclonal antibody called tremelimumab announced its Orphan Drug Designation for mesothelioma. Orphan drug status can help fast-track promising therapies for very rare diseases.
A recent study of tremelimumab for mesothelioma found that half of the patients tested achieved disease control for a median of 10.9 months. All were patients who had failed to respond to standard chemotherapy. In a press release, AstraZeneca said tremelimumab is now being tested in combination with other immunomodulators for the treatment of non-small cell lung cancer and head and neck cancer.
“The ability to unleash an efficient anti-tumor immune response by targeting regulatory immune checkpoint(s) with immunomodulatory monoclonal antibodies (mAbs), is leading to very promising clinical results in different tumor types,” note the Italian authors of a recent article entitled “Immune Checkpoint Blockade in Malignant Mesothelioma.” Their findings were published in the June issue of Seminars in Oncology.
Calabro, L and Maio, M, “Immune Checkpoint Blockade in Malignant Mesothelioma”, June 2015, Seminars in Oncology. Pp. 418-422
Manfield, Aaron, “Potential Applications of Immune Checkpoint Blockade for Mesothelioma”, January 28, 2015, Contemporary Oncology, OncLive website.