Is there a role for immune checkpoint blockade with ipilimumab in prostate cancer?

Abstract

Treatment for advanced prostate cancer has and will continue to grow increasingly complex, owing to the introduction of multiple new therapeutic approaches with the potential to substantially improve outcomes for this disease. Agents that modulate the patient's immune system to fight prostate cancer – immunotherapeutics – are among the most exciting of these new approaches. The addition of antigen-specific immunotherapy to the treatment of castration-resistant prostate cancer (CRPC) has paved the way for additional research that seeks to augment the activity of the immune system itself. The monoclonal antibody ipilimumab, approved in over 40 countries to treat advanced melanoma and currently under phase 2 and 3 investigation in prostate cancer, is thought to act by augmenting immune responses to tumors through blockade of cytotoxic T-lymphocyte antigen 4, an inhibitory immune checkpoint molecule. Ipilimumab has been studied in seven phase 1 and 2 clinical trials that evaluated various doses, schedules, and combinations across the spectrum of patients with advanced prostate cancer. The CRPC studies of ipilimumab to date suggest that the agent is active in prostate cancer as monotherapy or in combination with radiotherapy, docetaxel, or other immunotherapeutics, and that the adverse event profile is as expected given the safety data in advanced melanoma. The ongoing phase 3 program will further characterize the risk/benefit profile of ipilimumab in chemotherapy-naïve and -pretreated CRPC.

Messenger RNA vaccine based on recombinant MS2 virus‐like particles against prostate cancer

“…Over the past decades, several therapeutic approaches for PCa including chemotherapy, radiotherapy, surgery and immunotherapy provide survival benefits. The most attractive approach is immunotherapy that modulate the patient's immune system to fight PCa, including monoclonal antibodies ( e.g ., Ipilimumab, augmenting immune responses to tumors by blockade of cytotoxic T‐lymphocyte (CTL) antigen 4, dendritic cells (DCs) vaccines ( e.g ., Sipuleucel‐T, presenting the epitopes of prostate acid phosphatase (PAP) to CTLs through activated DCs, viral vector vaccine ( e.g ., Prostvac, a prostate‐specific‐antigen‐directed vaccine, DNA vaccines and RNA vaccine ( e.g ., CureVac, a free and protamine‐complexed mRNA vaccine. Among these modalities, mRNA vaccine is considered as an efficient alternative to protein and DNA vaccines not only because of its antigenic potential and immunostimulating property but also because mRNA is safe, low cost, highly pure and prepared easily…”

Bispecific NKG2D-CD3 and NKG2D-CD16 fusion proteins for induction of NK and T cell reactivity against acute myeloid leukemia

“…NKG2D-CD3, in contrast, may constitute an optimal treatment for fit patients with higher leukemic burden. This notion is supported by the success of T cell mobilizing strategies that meanwhile have become a mainstay in oncological treatment: In solid tumors, blockade of inhibitory immune checkpoints like PD-1 und CTLA4 can induce remissions even in patients with progressed disease state [39–42]. Application of CART cells targeting CD19 is particularly effective in patients with lymphoid malignancies.…”

Immunotherapy for genitourinary cancer

“…Several studies evaluated ipilimumab in mCRPC as monotherapy or in combination with radiotherapy, docetaxel, or other immune therapeutics [145]. Kwon et al [146] conducted a randomized, multicenter, double-blind phase III trial comparing OS duration in patients with post-docetaxel mCRPC treated with ipilimumab or placebo, each following single-dose radiotherapy.…”