mRNA-Based Therapy for Prostate Cancer
The prostate is a small walnut-shaped gland in males that produces the seminal fluid that nourishes and transports sperm. Prostate cancer (PCa) occurs in the prostate and represents the leading cause of cancer in men. At present, there is no cure for metastatic castrate-resistant prostate cancer (CRPC), which highlights the need to identify novel and more effective therapies. In the era of immunotherapy, mRNA-based drug as an available vaccine strategy is an appealing treatment modality for the treatment of patients with prostate cancer. Creative Biogene is a forward-looking research institute as well as a leading custom service provider in mRNA-based drug research and development (R&D). Our team is experienced in the customized synthesis of mRNA, mRNA optimization, and mRNA delivery system development. We are devoted to offering high-quality service and achieving the best outcome for our customers from all over the world.
Emerging therapeutic targets for PCa
Prostate cancer (PCa) remains the second-commonest cancer in men, with a lifetime incidence of about 15–20%. Many prostate cancers grow slowly and are confined to the prostate gland, where they may not cause serious harm. For early stage prostate cancer, the management of localized (such as surgery or radiotherapy) is effective and the survival rates are high. However, other types of PCa are aggressive and can spread quickly. Currently, metastatic PCa is an incurable condition. Fortunately, the pace and breadth of preclinical discovery and clinical research have recently accelerated in the PCa setting, along with a substantial number of new agents. Based on various cell signaling, epigenetic enzymatic, and DNA repair pathways, several novel, small-molecule inhibitors for the treatment of PCa are being evaluated, such as enhancer of zeste homologue 2 (EZH2), poly ADP-ribose polymerase (PARP), and tyrosine kinase inhibitors. In addition, multiple vaccines are being developed for patients with PCa, including CV9104, DCVAC/PCa, PROSTVAC-V/F, MVI-816, and PF-06753512.
mRNA-based therapy for PCa
Anticancer-vaccine strategies in PCa
Given the recent successful investigation of immunotherapeutic approaches in numerous solid and hematological malignancies, this therapy is being explored widely in the PCa arena. One of the reasons PCa has been amenable to the development of specific immunotherapeutic and vaccination approaches is that several tumor-associated antigens (TAAs) are overexpressed on PCa cells. These TAAs, such as prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and prostate-specific membrane antigen (PSMA) can be specifically targeted by activated immune cells (cytotoxic T lymphocytes, CTLs), which is a part of an immune-mediated anti tumor response. Since the TAAs are only present in tumors but not in healthy tissues, the antigens might offer ideal targets for immunotherapy, especially suitable for patients after radical prostatectomy (RP).
mRNA-based therapy vaccination strategies for PCa
mRNA as the technological basis of therapeutics and vaccines, not only has strong safety as well as efficient protein expression but also offers high flexibility with respect to its production and application. CV9103 and CV9104 are mRNA-based vaccines that target a number of different TAAs. CV9103 encodes for PSA, PSMA, prostate stem cell antigen (PSCA), and six transmembrane epithelial antigens of prostate 1 (TEAP1). While CV9104 targets STEAP1, PSA, PSMA, PSCA, PAP, and MUC1. The mRNAs are complexed with protamine to enhance the immunogenicity of the expressed proteins. Clinical phase I/IIa study of CV9103 in CRPC showed good tolerability and favorable immune-activation. In a randomized phase IIb study of CV9104, results showed that CV9104 had no significant impact on overall survival (OS) or progression free survival (PFS) after multiple vaccine administrations. Therefore, further studies will reassess the method of administration as well as a formulation for CV9104. In addition, a combination of this mRNA vaccine with immune checkpoint inhibitors will be investigated, aiming to induce further tumor-related immune stimulation.
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References
- Saad, F., et al. (2019). "Emerging therapeutic targets for patients with advanced prostate cancer." Cancer treatment reviews, 76, 1-9.
- Handa, S., et al. (2020). "Immunotherapy in prostate cancer: current state and future perspectives." Therapeutic Advances in Urology, 12, 1756287220951404.
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