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Immunotherapy for mesothelioma is a type of cancer treatment that aims to fight the progression of cancer by stimulating the immune system’s ability to target and attack tumor cells. This type of treatment is sometimes called “biologic therapy” or “biotherapy.”[1]
Research shows that certain forms of immunotherapy can be effective at reducing the growth of MPM in patients who have relapsed after chemotherapy treatment.[2] A study in patients receiving nivolumab (Opdivo), some with ipilimumab (Yervoy), found that as many as half did not progress in their symptoms during the 12 week observation period.
Aside from nivolumab and ipilimumab, common immunotherapy drugs for mesothelioma include:
- CRS-207
- Amatuximab
- SS1P
- Keytruda (Pembrolizumab)
CRS-207
CRS-207 is an immunotherapy drug developed by Aduro Biotech intended to provoke a strong immune response against cancer cells in patients with mesothelioma, ovarian cancer, and gastric cancer.
The mechanism of the drug acted like a vaccine; samples of heavily modified Listeria monocytogenes bacterial cells were injected into patients with the idea that they could help “train” the immune system to attack mesothelin, a tumor-associated antigen (TAA) that is often overproduced by tumors.[3]
Initial Phase 1 studies were promising, and studies in mice indicated that CRS-207 could achieve a higher response rate when combined with the immunotherapy drug Keytruda.[4]
However, Phase 2 clinical trials were abruptly cancelled as a result of low enrollment and the fact that many patients showed no measurable response to CRS-207.[5] The drug is considered safe, based on the results of its trials, but has not yet demonstrated itself to be effective. More research is needed to determine its clinical value.
Amatuximab
The immunotherapy drug amatuximab (MORAb-009) targets mesothelin proteins, which tend to be overexpressed by tumor cells in mesothelioma and other cancers. The drug is, “a mouse-human chimeric monoclonal antibody with a selective affinity for MSLN [mesothelin].” [6]
Studies of amatuximab in individuals with mesothelioma have been limited, with one clinical trial cancelled for lack of business funding.[7] A combination of amatuximab with the chemotherapy drugs pemetrexed and cisplatin was used in a clinical trial, which revealed that the addition of the immunotherapy drug had no significant impact on patient survivability or cancer growth.[8]
The drug is currently being studied to determine its effects and effectiveness in individuals diagnosed with mesothelioma.
SS1P
SS1P is a type of cancer immunotherapy drug that can potentially treat mesothelioma. Like CRS-207 and amatuximab, it attempts to train immune system cells to target mesothelin proteins that tend to be overexpressed in certain tumors, including those created by mesothelioma. This particular mesothelin targeter attaches mesothelin proteins to partial bacterial DNA components, potentially “training” immune cells to attack mesothelin more readily.[9]
Trials in mice reveal that SS1P can not only bring about the death of cancer cells but reduce the risk of new cancer cell formation.[10] Studies in humans have predominantly combined SS1P with other drugs, like pentostatin and cyclophosphamide, and they show some promise for managing cancer growth.[11],[12]
Keytruda (Pembrolizumab)
Keytruda (generic name pembrolizumab) is a immunotherapy drug that can be used to treat mesothelioma. It works by targeting the surface receptor PD-1, which can in turn trigger T-cells to attack and kill cancer cells.[13]
Trials in humans compared pembrolizumab with the effect of the chemotherapy drugs cisplatin and pemetrexed, which are currently the only agreed-upon first-line treatment for patients with mesothelioma. The trials revealed that pembrolizumab can be safe, but it was found to be equally as effective as chemotherapy drugs.[14]
This outcome suggests that pembrolizumab can be an alternative to chemotherapy treatments according to the preferences or tolerances of certain patients.[15] Other studies suggest that pembrolizumab could show additional effectiveness when combined with chemotherapy, especially as a second-line treatment for patients who do not respond to first-line therapy.[16]
[1] https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html
[2] https://www.asco.org/about-asco/press-center/news-releases/early-research-suggests-first-immunotherapy-mesothelioma
[3] https://immuno-oncologynews.com/crs-207/
[4] https://immuno-oncologynews.com/2019/03/27/phase-2-trial-crs-207-keytruda-combination-mpm-discontinued/
[5] https://clinicaltrials.gov/ct2/show/NCT03175172
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687483/
[7] https://clinicaltrials.gov/ct2/show/NCT02357147
[8] https://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.TPS8577
[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265108/
[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265743/
[11] https://cancerres.aacrjournals.org/content/74/11/2907
[12] https://ascopubs.org/doi/10.1200/JCO.2016.68.3672
[13] https://www.cancer.gov/publications/dictionaries/cancer-drug/def/pembrolizumab
[14] https://www.sciencedaily.com/releases/2019/09/190930082253.htm
[15] https://www.medscape.com/viewarticle/919193
[16] https://www.ncbi.nlm.nih.gov/pubmed/30142389
