How effective is immunotherapy in managing prostate cancer?

Avishek Roy

Scientific Liaison Manager
4baseCare

Precision oncology and immunotherapy are reshaping the cancer treatment landscape. Precision oncology focuses on gene-directed, histology-agnostic therapies that are customized to each patient based on biomarker analysis, as well as immunotherapy. Our immune system has a unique ability to destroy cells that are potentially harmful, such as infected or cancerous cells. However, in most patients with progressing cancer, anti-cancer immune responses either never developed or have been turned off by the cancer. The remarkable capacity of cancer cells to reprogram themselves after therapy and hide from the immune system has long been a difficulty with treating cancer. Hacking the immune system and reprogramming immune cells to respond to cancer cells that are dysfunctional is one strategy to combat cancer. Immunotherapy holds the potential of allowing doctors to programme the body to be smarter than the tumor and engage the immune system to destroy the cancer. Immunotherapy, also known as biologic treatment, aims to boost a person’s immune system so that it can eradicate any prostate cancer cells present in the body. Several current clinical studies are being undertaken throughout the world to improve prostate cancer immunotherapy.

Immunotherapy fights cancer by utilizing the patient’s own immune system. The FDA has approved Sipuleucel-T (Provenge), a cell-based prostate cancer vaccination, for men with metastatic prostate cancer who are resistant to hormone treatment. This medication is for individuals, who have little or no pain, and it’s usually given before chemotherapy, however it seems to work in some men even after chemotherapy. PROVENGE is a personalized immunotherapy that completely stimulates immune cells, making it easier for the body to identify prostate cancer cells as aberrant cells, and has been shown in clinical studies to prolong the survival of specific patients.. Prostatic acid phosphates or PAP, is an antigen expressed by 95 percent of prostate cancer cells. PROVENGE aids immune cells in identifying and attacking cells that express PAP.

The personalization process involves extracting the white blood cells (immune cells) and then stimulated to programme T cells (a kind of white blood cell known as lymphocytes) to attack prostate cancer cells. Three days later, the newly activated cells are returned and reintroduced into the person. On a bi-monthly basis, this injection process is done three times. There is a low risk of rejection because the blood cells are provided by the patient. Flu-like symptoms that last around 24 hours are the most prevalent adverse effects. The real-world usage of PROVENGE in males with asymptomatic or mildly symptomatic mCRPC was investigated in a several-year study (named PROCEED), which included thousands of patients. PROVENGE was proven to extend life in men with mCRPC.  According to findings from the large real-world PROCEED trial, men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (mCRPC) and baseline prostate-specific antigen (PSA) levels 5.27 ng/mL had a median overall survival (OS) approaching 4 years with sipuleucel-T (PROVENGE) treatment. The FDA has approved Sipuleucel-T for males with mCRPC of any race.

A current immunotherapeutic approach is the application of checkpoint inhibitors, which prevent the inhibition of a T cell-based immune response. Pembrolizumab (KEYTRUDA), a checkpoint inhibitor, targets the protein PD-1, which is located on T cells, which are immune cells. KEYTRUDA increases the immune system’s response to prostate cancer cells by inhibiting PD-1 on your T cells. KEYTRUDA was approved by the FDA in 2017 for the treatment of all solid tumors, including prostate cancer that have mutations in mismatch repair genes (MMR), exhibit microsatellite instability (MSI) in the tumor and/or have a high tumor mutational burden (TMB-H). Once every three weeks, pembrolizumab is given intravenously. Fatigue, cough, shortness of breath, nausea, diarrhoea, itching, rash, and decreased appetite are the most prevalent adverse effects. Since it modifies the immune system, it can induce uncommon but significant adverse effects such as hyperactive immune responses, which are usually addressed by discontinuing the medicine and, in some circumstances, initiating steroid treatments to decrease the immune responses. Combination immunotherapy treatments in patients with mCRPC, resulted in modestly greater anti-tumour activity. Pembrolizumab was introduced to enzalutamide in a phase 2 trial for males with mCRPC who were advancing on enzalutamide, and five (18%) of 28 patients had a PSA drop equal to or higher than 50%.

New immunotherapy therapies for prostate cancer are still being developed, and the indications for using the present prostate cancer vaccination are being expanded. PROSTVAC and Yervoy are two drugs that are currently being investigated. PROSTVAC is a virus-based vaccination that has proved to be effective in men with castrate-resistant metastatic prostate cancer. It would function similarly to Provenge, but without the need to adapt the medicine to the immune system of each individual. PROSTVAC monotherapy is currently undergoing testing in phase II studies to prevent tumour relapse after surgery or in patients with biochemically recurrent prostate cancer. The monoclonal antibody Yervoy (ipilimumab) is being tested in hormone-resistant prostate cancer.

One of the most promising treatments in recent years is chimeric antigen receptor modified-T cells (CAR-T) cell treatment, a sort of immunotherapy that exploits and boosts the immune system’s natural potential. T-cells from the participant are harvested and genetically modified (CAR T) to detect particular molecules expressed on the surface of cervical cancer cells, after which they are returned to the participant by intravenous infusion. Once within the body, CAR T cells can multiply to enormous numbers, remain for long periods of time, and provide continued tumour suppression as well as potential recurrence prevention. Various CAR T cell products are under investigation in preclinical studies and in clinical trials for prostate cancer. A number of prostate cancer-relevant antigens have been targeted by these CAR T cell approaches, including PSCA, PSMA and EpCAM. CAR T cell immunotherapy is an intriguing advancement in oncology that has the potential to become a cornerstone of prostate cancer treatment in the future.