Cancer immunotherapy began in 1891, when William Coley was the first to try and harness the immune system to treat cancer. Since then, immunotherapy has become a mainstay of cancer treatment and is used to fight many 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 seen as a revolutionary cancer treatment decades final.
In addition to immune checkpoint inhibitors, significant cancer immunotherapy treatments also include cancer vaccines and cell therapies. Immune checkpoint inhibitors and vaccines are primarily approved in the treatment of solid tumors, whereas cell therapy – although also being explored for solid malignancies – has proven highly effective for treating blood cancer, with six different CAR-T cell therapies already approved by the Food and Drug Administration (FDA) US since 2017.
In this article we look at five types of cancer that immunotherapy has the potential to cure.
Immunotherapy for bladder cancer
Immunotherapy has been used to treat bladder cancer since the Bacillus Calmette-Guerin (BCG) vaccine – an intravesical immunotherapy containing attenuated Mycobacterium bovis bacteria – was first approved by the FDA in 1990 for early bladder cancer, known as non-bladder cancer. muscle invasive. 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 immune system cells to grow and become active in the lining of the bladder, making it effective against bladder cancer. It is still used as standard treatment for non-muscle invasive bladder cancer and is very effective at stopping or delaying the cancer from growing back or spreading to the deeper lining of the bladder.
However, for non-muscular invasive cancers that do not respond to treatment with BCG, the FDA recently approved the first adenoviral vector-based gene therapy called Nadofaragene firadenovec (Adstiladrin), which consists of a virus that contains the gene for making interferon. alpha-2b – an important immune system protein. This sends a gene into the cells that line the bladder wall, causing these cells to make extra interferon alpha-2b, which then helps the immune system attack cancer cells.
Although most bladder cancers – about 75% – diagnosed at an early stage when a treatable cancer, some spread beyond the lining of the bladder and into the surrounding muscles. Immune checkpoint inhibitors, such as avelumab (Bavencio) and nivolumab (Opdivo), could 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 to their partner proteins on tumor cells. This prevents a ‘die’ signal from being sent to the T cells, which allows them to recognize and destroy cancer cells.
Immunotherapy for esophageal cancer
The two main types of esophageal cancer are squamous cell carcinoma, which starts in the flat cells that line the esophagus, and adenocarcinoma, which starts in the cells that make and secrete mucus. Chemotherapy is the current standard of treatment for esophageal cancer, but the overall five-year survival rate for esophageal cancer is only about 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 be used alone or in combination with chemotherapy. Immune checkpoint inhibitors are the main type of immunotherapy approved to treat esophageal cancer, and include the PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab, and the CTLA-4 inhibitor ipilimumab (Yervoy).
According to clinical trial results in 2021, two immunotherapy-based combination therapies were found to be more effective than chemotherapy alone for some patients with advanced esophageal cancer, and increase how long patients live for 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 – cancer of the lymphatic system – are Hodgkin’s lymphoma, which affects 10% of patients, and non-Hodgkin’s 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 began in 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 the lymphoma drug Genentech Polivy (polatuzumab vedotin-piiq) for use in combination with rituximab.
Meanwhile, CAR-T cell therapy is a new type of treatment for lymphoma, and has shown very promising results in non-Hodgkin’s lymphoma patients who relapsed or did not respond to other therapies. Several CAR-T cell therapies have now been approved by the FDA for this. This therapy has been approved for: aggressive recurrent or refractory large B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, and transformed follicular lymphoma; relapsing or refractory mantle cell lymphoma; and relapsed or refractory follicular lymphoma.
Immunotherapy for multiple myeloma
Multiple myeloma is a cancer that forms in the white blood cells known as plasma cells in the bone marrow and is very difficult to treat. It is a challenge to develop immunotherapy treatments that successfully recognize and kill myeloma cells because they need to overcome the myeloma’s ability to hide from and/or weaken the immune system.
However, there are several approved immunotherapies for multiple myeloma. The first three immunotherapies approved for multiple myeloma were antibody-based immunotherapies, all approved for a subset of patients with advanced multiple myeloma: Daratumumab (Darzalex) – a monoclonal antibody that targets the CD38 pathway; isatuximab (Sarclisa) – a monoclonal antibody that also targets the CD38 pathway; and Elotuzumab (Empliciti) – a monoclonal antibody that targets the SLAMF7 pathway.
Recently, CAR-T cell therapy has also been approved for use in a subset of patients with advanced relapsed or refractory multiple myeloma, and there are more clinical trials under way to approve 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 mainly treated with surgery and chemotherapy, with immunotherapy – that is, immune checkpoint blockers – only occasionally being used as an adjunct treatment for patients with advanced ovarian cancer.
This is because immunotherapy has not been shown to be as successful in the treatment of ovarian cancer as it is for other types of cancer, because ovarian cancer is very good at tricking the immune system into not attacking it. It is also estimated that about 80% of people with ovarian cancer are not diagnosed until the cancer has spread beyond the ovaries, making treatment choices more difficult.
However, there have been few clinical trials conducted around the use of immunotherapy for ovarian cancer. Some are focused on using immune checkpoint inhibitors in combination with chemotherapy and other types of cancer drugs, while others are focused on developing a vaccine to treat ovarian cancer.
For example, UK-based biopharma company Oxford Vacmedix recently completed phase 1a clinical trials 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 enables unregulated growth – and stimulates an immune response.