Medical Information

Immunotherapy

Minggui Pan, MD, PhD

Chief, Department Of Oncology-Hematology at Kaiser Permanente Medical Center

Board of Director at New Hope Chinese Cancer Care Foundation

Chinese translation: Rosalyn Lim, RNP, CNM

 

What is cancer immunotherapy?

Cancer immunotherapy refers to combating malignant cells by increasing their immunity against cancer cells. There are currently several types of immunotherapy that have been approved for marketing or are under development. One of these, known as checkpoint inhibitors, has received attention and coverage from various media. Another type of immunotherapy, called CAR-T technology, is also under rapid research and development.

What is an immune checkpoint?

Checkpoints are key steps in the regulation of biological responses. For example, in the case of an immune response, immune checkpoints ensure that our body’s organs, tissues, or cells are not attacked by our own immune system, and that humans respond to external attacks (such as Viral infection, etc.) Our immune system is constrained by checkpoints without overreaction.

The tumor cells use this originally normal immunomodulatory property to evade the attack of immune cells. Tumor cells bind to the PD-1 (programmed death-1) protein on the surface of T cells through a protein called PD-L1 (programmed death ligand-1) on their surface to brake T cells. “To prevent these T cells from being activated to weaken or even stop attacking tumor cells.”

What is an immune checkpoint inhibitor?

Immune checkpoint inhibitors are antibody drugs developed using the concept of blocking PD-1 or PD-L1 to reactivate T cells that are inhibited by tumor cells. After these T cells are reactivated, they have the ability to attack tumor cells. Normally, these T cells are already around the tumor cells (called tumor infiltrating T cells) and are only suppressed. The role of checkpoint inhibitors is to eliminate this repressed phenomenon and make T cells reactivated, thereby initiating human immune cells to attack tumor cells.

What is an FDA approved checkpoint inhibitor?

The U.S. Food and Drug Administration (FDA) has approved four immune drugs, and many others are in the midst of a burst. The four immune drugs are:

Ipilimumab (Yervoy) is approved for the treatment of melanoma.

Nivolumab (Opdivo) is approved for the treatment of melanoma, non-small cell lung cancer, kidney cancer and Hodgkin’s lymphoma.

Pembrolizumab (Keytrud) is approved for the treatment of melanoma, non-small cell lung cancer, and renal cancer; it has also recently been approved for the treatment of head and neck tumors.

Atezolizumab (Tecentriq) was recently approved for the treatment of bladder cancer.

For melanoma, about 40% of patients may have a therapeutic effect, but only about 20% of lung, kidney, bladder and head and neck cancers have a therapeutic effect. Sometimes the treatment effect will be slower. Some people may not seem effective at first, but after a while, the cancer condition can be controlled and enter the so-called stable period.

Can checkpoint inhibitors treat other cancers?

Yes, these drugs have proven to be effective against other types of cancer, such as triple-negative breast cancer and colorectal cancer with DNA microsatellite instability, but the FDA has not yet approved treatment for these cancers.

What are the common side effects of checkpoint inhibitors?

Most patients respond well to these drugs, but some patients may have serious side effects like autoimmune diseases, such as drug-induced pneumonia, abnormal liver function, diarrhea caused by inflammation of the intestines, dry mouth, and skin rash.

What is CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy)?

CAR stands for “Chimeric Antigen Receptor”, and CAR-T refers to a T cell receptor that has been genetically engineered to contain two artificial protein molecules that allow T cells to recognize specific antigens. When the modified T cells are exposed to the antigen, they can transmit stimulation signals to recognize the cancer cells and trigger the immune effect of T cells. Currently, engineered T cells that have been shown to be effective recognize B cells, which in turn can treat B-cell leukemia and lymphoma. Researchers are now working toward making improved T cells recognise other types of cancer cells. CAR-T has been shown to be effective in the treatment of relapsed B-cell leukemia and lymphoma, and is expected to be approved by the FDA in the next one to two years.