Cancer immunotherapy dates back to 1891, when William Coley became the first person to try and harness the immune system to treat cancer. Since then, immunotherapy has become the mainstay of cancer treatment and is being used in the fight against many different types of cancer.
When the first immune checkpoint inhibitor – which works by blocking checkpoint proteins to help the body recognize and attack cancer cells – ipilimumab, was approved in 2011, it marked a major breakthrough in cancer immunotherapy, and led to immune checkpoint inhibitors being viewed as the revolutionary cancer treatment of the last decade.
As well as immune checkpoint inhibitors, significant cancer immunotherapy treatments also include cancer vaccines and cell therapies. Immune checkpoint inhibitors and vaccines are mainly approved in the treatment of solid tumors, whereas cell therapies – although also being explored for solid malignancies – have proven to be very effective for treating blood cancers, with six different CAR-T cell therapies having been approved by the U.S. Food and Drug Administration (FDA) since 2017.
In this article we take a look at five different types of cancer that immunotherapy can potentially cure.
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Immunotherapy for bladder cancer
Immunotherapy has been used to treat bladder cancer ever since the Bacillus Calmette-Guerin (BCG) vaccine – an intravesical immunotherapy containing a weakened form of the bacterium Mycobacterium bovis – was first approved by the FDA in 1990 for early bladder cancer, known as non-muscle invasive bladder cancer. There are now several approved immunotherapies for bladder cancer, including cancer vaccines, targeted antibodies and immune system modulators.
BCG was originally developed as a vaccine against tuberculosis, but it was discovered that it also encourages cells of the immune system to grow and become active in the bladder lining, therefore, making it effective against bladder cancer. It is still used as a standard treatment for non-muscle invasive bladder cancer and is very effective at stopping or delaying cancers from growing back or spreading into the deeper layers of the bladder.
However, for non-muscle invasive cancers that do not respond to treatment with BCG, the FDA recently approved the first ever adenoviral vector-based gene therapy called Nadofaragene firadenovec (Adstiladrin), which is made up of a virus containing the gene to make interferon alfa-2b – an important immune system protein. It delivers the gene into the cells lining the bladder wall, resulting in these cells making extra interferon alfa-2b, which then helps the immune system attack the cancer cells.
Although most bladder cancers – around 75% – are diagnosed at an early stage when the cancer is treatable, some spread beyond the lining of the bladder and into the surrounding muscle. Immune checkpoint inhibitors, such as avelumab (Bavencio) and nivolumab (Opdivo), may potentially be used to treat bladder cancer that has spread. They work by blocking checkpoint proteins – in this case PD-L1 and PD-1 – from binding with their partner proteins on tumor cells. This prevents an ‘off’ signal from being sent to the T cells, which allows them to recognize and destroy the cancer cells.
Immunotherapy for esophageal cancer
The two main types of esophageal cancer are squamous cell carcinoma, which begins in flat cells lining the esophagus, and adenocarcinoma, which begins in the cells that make and release mucus. Chemotherapy is the current standard treatment for esophageal cancers, but the overall five-year survival rate for esophageal cancer is only around 20%.
With that in mind, immunotherapy has also started to emerge as a standard treatment for some forms of esophageal cancer in recent years, and can either be used alone or in combination with chemotherapy. Immune checkpoint inhibitors are the main type of immunotherapy approved to treat esophageal cancer, and include PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab, and CTLA-4 inhibitor ipilimumab (Yervoy).
According to the results of a clinical trial in 2021, two immunotherapy-based combination therapies were found to be more effective than chemotherapy alone for some patients with advanced esophageal cancer, and improved how long patients lived for by several months. The combination therapies evaluated in the trial, CheckMate 648 – which included 970 patients with advanced or metastatic esophageal squamous cell carcinoma – were nivolumab plus chemotherapy, and nivolumab plus ipilimumab.
Immunotherapy for lymphoma
The two main types of lymphoma – a cancer of the lymphatic system – are Hodgkin lymphoma, which affects 10% of patients, and non-Hodgkin lymphoma, which affects 90%. There are currently many approved immunotherapy options for both types of lymphoma, including immune checkpoint inhibitors, monoclonal antibodies, immunomodulating drugs, and CAR-T cell therapy.
Immunotherapy for lymphoma has a long history and dates back to 1997 when the FDA approved an anti-CD20 monoclonal antibody called rituximab. Since then, several second and third generation anti-CD20 antibodies have also been developed, such as ublituximab and ofatumumab. Recently, the FDA approved Genentech’s lymphoma drug Polivy (polatuzumab vedotin-piiq) to be used in combination with rituximab.
Meanwhile, CAR-T cell therapy is the newest type of treatment for lymphoma, and has shown very promising results in patients with non-Hodgkin lymphoma who have relapsed or not responded to other therapies. Several CAR-T cell therapies have now been approved by the FDA for it. These therapies have been approved for: aggressive relapsed or refractory large B-cell lymphoma including diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, and transformed follicular lymphoma; relapsed or refractory mantle cell lymphoma; and relapsed or refractory follicular lymphoma.
Immunotherapy for multiple myeloma
Multiple myeloma is a cancer that forms in white blood cells known as plasma cells in bone marrow and is notoriously difficult to treat. It has been a challenge to develop immunotherapy treatments that successfully recognize and kill myeloma cells because they need to overcome myeloma’s ability to hide from and/or weaken the body’s immune system.
However, there are several approved immunotherapies for multiple myeloma.The first three approved immunotherapies for multiple myeloma were antibody-based immunotherapies, all approved for subsets of patients with advanced multiple myeloma: daratumumab (Darzalex) – a monoclonal antibody targeting the CD38 pathway; isatuximab (Sarclisa) – a monoclonal antibody also targeting the CD38 pathway; and Elotuzumab (Empliciti) – a monoclonal antibody targeting the SLAMF7 pathway.
Most recently, CAR-T cell therapies have also been approved for use in subsets of patients with advanced multiple myeloma that has relapsed or is refractory, and there are more clinical trials underway looking to approve various different types of immunotherapy for this type of cancer.
Immunotherapy for ovarian cancer
According to the American Cancer Society (ACS), ovarian cancer is the fifth leading cause of cancer death in women. It is primarily treated with surgery and chemotherapy, with immunotherapy – namely immune checkpoint inhibitors – only sometimes being used as an add-on treatment for patients with advanced ovarian cancer.
This is because immunotherapy has not yet proven to be as successful in the treatment of ovarian cancer as in other cancer types, due to ovarian cancers being particularly good at tricking the immune system into not attacking it. It is also estimated that around 80% of people with ovarian cancer are not diagnosed until the cancer has already spread beyond the ovaries, making treatment options even more difficult.
However, there are several clinical trials being conducted surrounding the use of immunotherapy for ovarian cancer. Some are focusing on using immune checkpoint inhibitors in combination with chemotherapy and other types of cancer drugs, while others are focused on developing vaccines to treat ovarian cancer.
For example, U.K. based biopharma company Oxford Vacmedix recently completed its phase 1a clinical trial of its lead cancer vaccine, OVM-200, for the treatment of ovarian cancer, as well as non small cell lung cancer (NSCLC) and prostate cancer. OVM-200 targets survivin – a protein overexpressed by cancer cells that allow unregulated growth – and stimulates an immune response.