From the Guidelines
Immunotherapy for prostate cancer is primarily represented by Sipuleucel-T, an autologous cancer "vaccine" that has been approved by the FDA since 2010.
Key Points
- Sipuleucel-T involves the collection of a patient's white blood cell fraction, exposure to the prostatic acid phosphatase-granulocyte macrophage colony-stimulating factor (PAP-GM-CSF) recombinant fusion protein, and subsequent reinfusion of the cells 1.
- The treatment has been shown to result in a 22% reduction in mortality risk (HR, 0.78; 95% CI, 0.61–0.98; P=0.03) in patients with minimally symptomatic or asymptomatic metastatic castration-resistant prostate cancer (mCRPC) 1.
- Common complications include mild to moderate chills, pyrexia, and headache, which are usually transient 1.
- The panel recommends using Sipuleucel-T as initial therapy for asymptomatic or minimally symptomatic patients with metastatic CRPC, as disease burden is lower and immune function is potentially more intact 1.
- It's essential to note that usual markers of benefit, such as decline in PSA and improvement in bone or CT scans, are not seen with Sipuleucel-T treatment, making it challenging to ascertain individual patient benefit using currently available testing 1.
From the Research
Definition and Overview of Immunotherapy for Prostate Cancer
- Immunotherapy is a treatment modality that has shown promising therapeutic effects in various cancers, including hematological malignancies and certain solid tumors 2, 3, 4, 5, 6.
- However, prostate cancer is considered an immune-resistant "cold" tumor, which limits the efficacy of immunotherapy in patients with solid tumors 2, 4, 5.
Mechanisms and Challenges of Immunotherapy for Prostate Cancer
- The tumor microenvironment in prostate cancer is characterized by few tumor-infiltrating lymphocytes, abundant immunosuppressive cells, low immunogenicity, and a noninflammatory phenotype, which significantly influences the efficacy of immunotherapy 2, 4.
- Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer 4.
Therapeutic Advances and Strategies in Immunotherapy for Prostate Cancer
- Various immunotherapy strategies are being evaluated for prostate cancer, including immune checkpoint inhibitors, bispecific T cell-engaging antibodies, chimeric antigen receptor (CAR) T cells, therapeutic vaccines, and cytokines 3, 4, 5.
- Combining various classes of treatment modalities, such as vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody-drug conjugates, or chemotherapy, may enhance immune responses and induce long-lasting clinical responses without significant toxicity 4, 5.
- Identifying new immunotherapeutic targets and designing personalized immunotherapy strategies based on patient-specific molecular signatures are crucial to improve the efficacy of immunotherapy for prostate cancer 5.