Immunotherapy For Prostate Cancer

Introduction 

Prostate cancer is one of the most common cancers in people assigned male at birth (AMAB), except for skin cancer, in the United Kingdom. The cancer begins in the prostate gland and develops slowly. The symptoms usually appear until it starts to affect the urethra (the tube that carries urine out of the penis).

The prostate is a small gland in the pelvis and is primarily responsible for creating fluids in your semen and pushing your semen through the urethra when you ejaculate. 

The exact cause of prostate cancer in AMAB individuals is not fully understood but it's likely to be a variety of factors that increase your chances of developing cancer such as age, family history, ethnic group, diet and obesity. 

A wide range of effective treatments are used to control the progression of the disease and prolong life. The type of treatment you require will depend on your circumstances. 

In this article, we will discuss a type of treatment that uses the patient’s immune system to target cancer cells, known as immunotherapy. 

Understanding prostate cancer 

As with all cancers, prostate cancer begins when cells grow uncontrollably and spread into the surrounding tissue. The tumours in AMAB individuals with prostate cancer grow so slowly that they may not cause any problems in patients daily lives. This means that you may never require treatment. Your doctor may suggest watchful waiting or active surveillance, an approach that involves careful monitoring of your condition and beginning treatment if your condition gets worse. 

More than 80% of men diagnosed with prostate cancer survived their disease after ten years. This is because effective diagnostic tools like PSA testing have diagnosed the disease earlier and effective treatments are associated with higher survival. 

Common treatment methods

Treatment aims to slow disease progression, improve quality of life and reduce mortality. These include:

• Radical prostatectomy (surgical removal of the prostate gland)
• Radiotherapy
• Brachytherapy
• Hormone therapy 
• Chemotherapy
• Immunotherapy

If you show signs of disease progression, your doctor will discuss the benefits and risks and decide the most appropriate treatment for your circumstances. Doctors will consider your preferences, any underlying health condition and your general health.

Basics of Immunotherapy 

Definition and principles of immunotherapy 

Immunotherapy has been an effective treatment for patients with prostate cancer by using the patient’s immune system to fight against cancer cells. There’s a wide range of mechanisms that target cancer cells and have been shown to prolong life.¹ The response to immunotherapy can vary from person to person.

How immunotherapy differs from traditional treatments 

Many traditional treatments for cancer target cancer cells, but these may also target your normal and healthy cells, which can bring unpleasant symptoms. In contrast, immunotherapy aims to encourage your immune system to fight cancer cells, Immunotherapy only targets your immune system, not all the cells in your body, so you may feel fewer side effects. 

Key components of the immune system involved

The role of the immune system is to prevent you from feeling unwell and promote healing while you're sick or injured. The key components of the immune system include:

• T-cells and B-cells (white blood cells) – originate from the bone marrow
• Antibodies
• Lymphatic system
• Complement system
• Spleen
• Thymus 

These components work together to defend the body against pathogens. Immunotherapy helps our immune system to fight against cancer. There are many ways the immune system can recognise and fight cancer cells.²

Immunotherapy approaches for prostate cancer 

Checkpoint inhibitors

The role of immune checkpoint inhibitors (ICIs) is to ensure healthy cells are not destroyed by a strong immune response. When a tumour cell binds with a T-cell, it sends an “off” signal so that the immune system is prevented from destroying the cancer cell.

Checkpoint inhibitors work by preventing the “off” signal from being sent to the T-cell. When this happens, it allows the T-cells to destroy the cancer cells.

Role of checkpoint inhibitors in prostate cancer 

Researchers have found that prostate cancer has a low number of T-cells in the tumour tissue, meaning a poor response to checkpoint inhibitors. ICIs will work best if there are T-cells in the tumour tissue. In early clinical trials, ICIs did not demonstrate the same level of success in prostate cancer in comparison to other types of cancer such as lung cancer.³

However, emerging research and ongoing clinical trials are exploring the potential to combine ICI therapy with other ICI drugs, as well as discovering new predictive biomarkers which are used to measure the likelihood that cancer will respond to treatment to improve ICI effectiveness.³

FDA-approved ICIs

The only FDA-approved ICI for prostate cancer is pembrolizumab. It targets and blocks the protein PD-1, triggers T-cells and kills the cancer cell.⁴

CAR-T Cell Therapy

Chimeric antigen receptor T-cell (CAR-T) therapy is effective against cancers that are resistant to traditional treatments. A doctor will take a sample of your blood and give it to scientists who can genetically engineer your T-cells so they can bind to specific proteins (antigens) on cancer cells and kill them.

CAR-T therapy is typically used to treat leukaemia, lymphoma and other blood system tumours. However, it is less effective in prostate cancers and other solid tumours. Fortunately, ongoing clinical trials are evaluating the safety and efficacy of CAR-T therapy for metastatic castration-resistant prostate cancer.⁵

Cancer vaccines

You may already be familiar with vaccines if you’ve received them from a young age. Unlike vaccines that are taken to prevent disease, cancer vaccines are taken when a patient already has cancer. The aim is to boost your immune system to recognise specific proteins on the surface of cancer cells (antigens) as foreign or abnormal.⁶ Several potential vaccines have been explored for the treatment of prostate cancer and these include:

Dendritic cell vaccines

Dendritic cells are a type of immune cell that presents antigens to other immune cells to initiate the immune response. Dendritic cell vaccines are made of dendritic cells with tumour antigens. This process is intended to enhance the immune response against prostate cancer cells.

The sapuleucel-T vaccine is an FDA-approved immunotherapy to treat asymptomatic or mild symptomatic castrate-resistant prostate cancer.⁷

Whole-cell vaccines

Whole-cell vaccines can also be described as a non-antigen-specific vaccine. This means it does not target a specific antigen. The goal is to expose the immune system to inactivated prostate cancer cells or small cell fragments t to stimulate an immune response.

Since the vaccine exposes the immune system to a variety of antigens, they may be particularly relevant for treating tumours that express distinct antigens, especially considering variations among different individuals.⁷

DNA vaccines

This type of vaccine uses your DNA or RNA that encodes prostate cancer antigens. DNA vaccines can generate strong anti-tumour cellular immune responses against tumour antigens.⁷

Challenges and limitations 

Side effects of immunotherapy 

Not everyone will experience all the side effects listed and the severity can vary from person to person. The side effects you may experience will depend on the type of immunotherapy you receive. You may experience side effects including:

• Fatigue
• Skin reactions like rash, itching or changes in skin colour
• Fever, chills or muscle weakness
• Nausea
• Diarrhoea
• Autoimmune reactions
• Joint pains

It’s important to speak with your doctor about your side effects early so they can be better managed. Report any side effects to your doctor even if they’re minor. If left untreated the side effects can be severe and even life-threatening. You may be prescribed treatments to manage the side effects.

Summary

Immunotherapy aims to use the patient’s immune system to fight prostate cancer and other types of cancers. These include checkpoint inhibitors, CAR-T cell therapy and cancer vaccines.
Due to the limited number of T-cells in the tumour tissue, the patient’s response to immunotherapy may not be effective. Researchers are hoping to uncover more about the mechanism that causes the tumour to have a low number of immune cells, which is described as a “cold” tumour. They are finding ways to convert the tumour from a “cold” to a “hot” tumour where there is a high number of immune cells, making it responsive to immunotherapy.⁷ This area of research looks promising. There are ongoing clinical trials and immunotherapy may be combined with other traditional methods to prolong a patient’s life.