Types of immunotherapy

Immunotherapy is designed to help the immune system recognize that cancer cells are harmful and must be destroyed. There are many types of immunotherapy medicines that work in different ways to help the immune system identify cancer cells.

There is one FDA-approved immunotherapy for breast cancer, and others are available in clinical trials. Whether you’re eligible for an immunotherapy clinical trial will depend on your diagnosis and the characteristics of the cancer cells. Talk to your oncologist about your eligibility to receive immunotherapy or join a clinical trial exploring one.

In this section, you’ll learn more about the types of immunotherapy and some breast cancer medicines within each class.

Immune checkpoint inhibitors

The body has immune “checkpoints” that keep the immune system from destroying healthy cells. The checkpoints make it less likely the body will attack itself. But those checkpoints can also stop the immune system from using its disease-fighting abilities on cancer cells.

Immune checkpoint inhibitors are medicines that help the immune system recognize that cancer cells are different from healthy cells—and a threat to the body. Normally, proteins on the surface of the immune cells known as T-cells, such as the PD-1 protein, latch on to healthy cells’ partner proteins—also known as immune checkpoints. This essentially shuts off the T-cell response. The T-cell recognizes the cells as healthy and does not attack them.

But sometimes, cancer cells and normal cells surrounding the cancer can produce a large amount of these immune checkpoint proteins, such PD-L1. In this way, they can appear normal and protect themselves from the body’s immune response. Immune checkpoint inhibitors can block this effect, helping the T-cells to recognize and destroy the cancer cells.

Some immune checkpoint inhibitors that work by blocking the PD-1 or PD-L1 pathway have been used in breast cancer. These are:

• Pembrolizumab (Keytruda): This medication was first FDA approved in May 2017 for people with metastatic tumors or solid tumors that cannot be treated with surgery, and that grow in part because of problems that occur when DNA makes copies of itself. These tumors are referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). A special test must be done on the cells to determine if they have these traits. Breast cancer tumors don’t often have these features. In November 2020, pembrolizumab was FDA approved specifically for breast cancer, for use in combination with chemotherapy for metastatic triple-negative disease that tests positive for PD-L1. And in July 2021 it was also approved for use in early-stage breast cancers that have certain features suggesting they are high risk for recurrence. Pembrolizumab is being actively studied for other types of breast cancer.
• Atezolizumab (Tecentriq): In May 2019, the FDA approved atezolizumab for use in combination with chemotherapy for locally advanced tumors that can’t be removed with surgery and for metastatic triple-negative breast cancer. The tumor had to express the PD-L1 protein. However, in 2021, based on more clinical trial results, the drug’s manufacturer no longer recommended its use for metastatic triple-negative breast cancer. The results suggested that chemotherapy alone was equally effective in slowing the cancer’s growth. People already taking this therapy can continue taking it, but it is no longer being prescribed to people who haven’t gotten it before.

Vaccines

When we think about vaccines, we usually think about preventing diseases. Vaccines given in childhood are used to prevent a range of viral diseases such as measles, mumps, and chickenpox. Vaccines for viruses such as influenza and COVID-19 can lower the risk of infection and, even if someone is infected, lower the odds of serious illness. These vaccines work by helping your immune system recognize and attack these viruses if you are exposed to them.

Cancer vaccines do not prevent cancer but instead are used as part of treatment, after a person has been diagnosed. They work by helping your body recognize and attack cancer cells, which contain substances known as tumor-associated antigens. Cancer vaccines can prime the immune system to target these antigens and destroy cancer cells.

Vaccines can be made from your own tumor cells or from tumor-associated antigens that are common in a specific type of cancer. They also can be made from a special class of immune cells known as dendritic cells, which play a key role in immune response. Another type of cancer vaccine uses a virus that is harmful to cancer cells but not normal cells.

The goal of any cancer vaccine is to help your immune system notice the differences between breast cancer cells and healthy cells, which could help it fight the cancer.

No cancer vaccines are currently approved for breast cancer, but a few are under study. One example is the NeuVax vaccine for HER2-positive breast cancer, which contains small pieces of the HER2 protein combined with an immune-boosting substance.

CAR-T transfer therapy

T-cells are a type of white blood cell that protects the body from disease. In Chimeric Antigen Receptor T-cell (or CAR-T) transfer therapy, a person’s blood is drawn, the T-cells are removed from the blood sample, genetically changed to bind to cancer cells, and then the cells are multiplied in a lab to make more than the body could make on its own. Scientists also can change the T cells’ DNA to make the cells better at recognizing cancer. Then, the modified T-cells are put back inside the body with an infusion through a vein. Several CAR-T drugs have been FDA approved for the treatment of leukemia and lymphoma, and studies are underway in breast cancer.

One type of T-cell transfer therapy focuses on white blood cells called tumor-infiltrating lymphocytes, or TILs, that are found in or near some tumors. TILs can recognize the tumor, but there may not be enough of them to destroy it, or their activity may be suppressed by the cancer cells. The hope is that infusing large numbers of TILs can help the body destroy the cancer. In some studies, TILS are also genetically modified to improve targeting of the cancer cells.

TIL therapy is still being tested in clinical trials. It has proved useful in melanoma, cervical cancer, and some other cancers. The FDA has approved several CAR T-cell therapies for blood cancers. CAR T-cell therapies are also being evaluated in clinical trials for other types of cancer, including breast cancer. For example, trials are assessing the use of this therapy for metastatic HER2-positive breast cancer, as well as triple-negative breast cancer.

Immune system modulators

Immune system modulators are medicines that can boost part of the immune system to treat certain types of cancer or help the body deal with treatment side effects. Examples include:

• Cytokines: These proteins, which are made by white blood cells, can be used to spur the activity of certain types of white blood cells or boost their numbers and improve immune response. Examples include interleukins and interferons.
• Hematopoietic growth factors: These are types of cytokines that can boost the production of red blood cells, platelets, or white blood cells. This can be helpful when blood cells are destroyed by chemotherapy.
• Biological response modifiers: These treatments can stimulate the activity of the immune system; some can prevent cancers from forming the new blood vessels they need to grow.

Some existing drugs have been changed to improve immune responses. For example, the immune activating part of trastuzumab (Herceptin) has been modified to create the drug margetuximab (Margenza). In clinical trials, margetuximab given with chemotherapy for metastatic disease was superior to trastuzumab and chemotherapy, possibly because of its ability to engage the immune system.

No immunomodulators are approved to treat breast cancer, but many are being studied. For example, researchers are investigating whether treatments that block the CD47 signal on breast cancer cells might increase the effectiveness of existing therapies. CD47 is known as the “don’t eat me” signal, and it tells the immune system cells called macrophages not to surround and destroy the cancer cells. Blocking this signal may help treatments work better.