Immunotherapy uses one’s own immune system to fight cancer.
Among these, checkpoint inhibitors and monoclonal antibodies have revolutionized cancer treatment in the last decade.
1. Checkpoint inhibitors
Checkpoints are parts of the immune system and they help to prevent the immune responses from becoming too strong. PD1 is a checkpoint protein present on immune cells namely T cells. PD1 when attaches to a protein called PD L1 ( present on normal and cancer cells ), it prevents T cells from attacking the cancer cells. When these checkpoints are blocked by PD1 and PD L1 inhibitors, T cells can destroy the cancer cells better.
PD-1 inhibitors include Pembrolizumab, Nivolumab, Cemiplimab etc and PD-L1 inhibitors include Atezolizumab, Avelumab, Durvalumab etc.
CTLA-4 inhibitors are another group of immunotherapy. CTLA-4 is another protein on some T cells which acts as an ‘off switch’ to keep the immune system in check. Ipilimumab is an example of a CTLA-4 inhibitor.
Cancers of the Lungs, head and neck, urinary bladder, kidneys, liver, melanoma, triple-negative breast, colon, esophagus, stomach and some types of lymphoma are commonly treated by immunotherapy. There is a dramatic improvement of overall survival in responding patients after treatment with checkpoint inhibitors.
Checkpoint inhibitors are given as intravenous infusions are currently expensive therapy. Usually, they are better tolerated than cytotoxic chemotherapy even in the elderly population. The commonest side effects are fatigue, decreased appetite, chills, flu-like symptoms, muscle aches, arthritis, cough, headache etc. Immune-related side effects like hypo and hyperthyroidism, hypopituitarism, hepatitis, colitis, pneumonitis, pancreatitis can be seen infrequently and this can sometimes lead to serious complications if not intervened properly.
2. Monoclonal antibodies
Monoclonal antibodies and antibody-drug conjugates are immune system proteins made in the laboratory. They can help the immune system find the cancer cells by binding with certain targets to be subsequently destroyed by the immune system. They are a type of cancer targeted therapy. Examples of monoclonal antibodies are Rituximab ( which binds to a protein called CD 20 on B cells and is used in Non-Hodgkins lymphomas), Trastuzumab ( which bind to Her 2 neu proteins in Her2 neu positive breast cancers, gastric cancers etc), Blinatumomab ( which binds to both CD 19 and CD 3 proteins and is used in relapsed acute lymphoblastic leukemia). An example of the antibody-drug conjugate is Ado-trastuzumab emtansine which is used in Her2 positive breast cancers.
These drugs are given as intravenous infusions. The commonest side effects are infusion-related and include chills, fever, fatigue, muscle aches, and pains. Some monoclonal antibodies and antibody-drug conjugates like trastuzumab and Ado-trastuzumab emtansine can cause left ventricular failure and congestive heart failure very rarely.
3. Oncolytic virus therapy
This treatment uses a genetically modified virus which when injected into the tumour, enters the cancer cells and makes a copy of itself. This makes the tumour cells burst and die. The patient’s immune system is triggered by the proteins released by this and it targets all cancer cells in his/her body that have the same proteins.
The FDA approved T-VEC(Talimogene laherparepvec) in 2015 as a therapy for advanced melanoma that cannot be treated with surgery. This oncolytic virus therapy contains a modified version of the herpes simplex virus and the doctor injects T-VEC into areas of melanoma to destroy the tumour cells.
Side effects of oncolytic virus treatment include tiredness, fever, chills, nausea and pain at the injection site. Clinical trial is testing other oncolytic viruses for different cancers either alone or in combination with chemotherapy.
4. Chimeric Antigen Receptor ( CAR)T cell therapy
In CAR T-cell therapy, the doctor removes T cells from your blood and specific receptor proteins are added to these cells so that the receptor proteins allow T cells to recognize the cancer cells. The changed T cells are put back into the body. Once inside the body, they find and destroy cancer cells.
CAR T-cell therapy is currently approved in some Non-Hodgkin lymphomas, relapsed pediatric B cell ALL, relapsed multiple myeloma etc. The side effects are fever, confusion, low blood pressure and rarely seizures.
5. Cancer vaccines
The vaccines expose our immune system to a foreign protein called an antigen. This triggers the immune system to recognize and destroy that antigen or related substances. There are 2 types of cancer vaccines: prevention vaccines and treatment vaccines. Sipuleucel-T which is used in prostate cancer is an example of a treatment vaccine.
Among the above-mentioned immunotherapy modalities checkpoint inhibitors and monoclonal antibodies are either used alone or in combination with other therapies including cytotoxic chemotherapy. For example, when Pembrolizumab is added to chemotherapy in the first-line therapy in PD-L1 expressing cancers, the overall survival is doubled. This kind of results is unprecedented in the history of the management of malignant diseases.
This blog is authored by Dr. K. M. Parthasarathy, Senior Consultant – Medical Oncology, Dharamshila Narayana Superspeciality Hospital, Delhi