Ipilimumab for the treatment of metastatic prostate cancer

Abstract

Immunotherapy with checkpoint inhibitors is beginning to be recognized as a valid weapon for the treatment of metastatic prostate cancer (PCa) when chemotherapy fails. Ipilimumab (ipi) is a fully humanized monoclonal antibody that blocks the activity of CTLA4. It also has a molecular weight of 148 kDa and is water-soluble at physiological pH. Ipi was first approved by the FDA for the treatment of malignant melanoma and is currently being studied in metastatic castration-resistant prostate cancer, with promising early results. Areas covered: The aim of this review is to collate the most significant preclinical and clinical studies available that look at ipi to propose new strategies for the future. Expert opinion: Additional studies are required to reduce toxicity and increase the activity of ipi in PCa. A possible strategy is to combine ipi with standard anti-cancer therapeutics such as vaccines, PDL1 inhibitors, antiandrogen drugs, and chemotherapy agents. Several initial results have suggested that combination strategies are useful to increase the activity in mCRPC, even if the toxicity of the treatment can increase. The activity of combined treatments is still not predictable, but considering the ongoing studies, we believe that they have good potential that will lead to the discovery of an optimal therapeutic strategy.

Recent Advances in Prostate Cancer Treatment and Drug Discovery

“…Nonetheless, in view of the strong survival advantage provided by therapies with immune checkpoint inhibitors in different cancer types, the potential benefits of immunotherapy are also being evaluated in prostate cancer [ 42 , 148 ]. First studies with the anti-CTLA4 antibody ipilimumab showed some promising results in early clinical evaluations addressing prostate cancer patients, but no improved overall survival could be determined afterwards in larger studies [ 24 ], even though complete remission was observed in a few cases [ 149 ]. The anti-PD-1 antibody pembrolizumab is being investigated in two clinical trials and durable responses have already been reported in patients with metastasized prostate cancer [ 42 , 148 ].…”

“…Finally, the impressive effects seen with immunotherapies in melanoma and non-small cell lung cancer [ 23 ] have led to the evaluation of immune checkpoint inhibitors in CRPC as well ( Figure 1 ). Initial results with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody ipilimumab have not met expectations [ 24 ]. Early clinical studies with agents targeting programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) are currently ongoing.…”

The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?

“…miRNA dysregulation progress has a key role in prostate cancer [ 41 ]. Anti-VEGF therapy and combined chemotherapy treatments trigger apoptosis in cancer and, in particular, in prostate cancer [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ].…”

Long Non-coding RNAs as Important Biomarkers in Laryngeal Cancer and Other Head and Neck Tumours

“…In esophageal squamous cell carcinoma (ESCC), the expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8%, p < 0.05), and this observation correlated with advanced clinical stage ( p < 0.01) and lymph node metastasis ( p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro [39,40,41] (Table 1).…”