Can Your Body Fight Cancer? Exploring Cancer Immunotherapy

Introduction

Immunotherapy

Immunotherapy is the treatment of any disease condition with the aid of our immune system . Immune cells that have been activated or genetically modified are used to treat any particular medical condition . A type of Immunotherapy used to treat cancer is cancer immunotherapy.

Immune System

The immune system protects the body from the invasion of pathogens, allergens, and other foreign particles. It consists of immune cells and organs. These immune cells circulate throughout the body, and they mount an immune response when they encounter a disease causing agent or antigen. Our body will elicit an immune response only if it identifies the particle or cell as foreign. Some of the organs and cells of the immune system are B lymphocytic cells (B cells), T lymphocytic cells (T cells), macrophages, leucocytes, neutrophils, dendritic cells, spleen, thymus, and bone marrow.

Antigens are proteins that are present on the surface of all cells. This protein helps our body to identify a cell as foreign or self. If the immune system identifies a protein as self then it will not harm the cell. Generally, the body mounts an immune response against an antigen it identifies as foreign. These proteins are not present in the human body, so our body differentiates between our proteins and foreign proteins.

Cancer

The cells in our body undergo cell division to multiply and repair the damage caused in the body due to infection or injury. In general, cell division occurs in a regulated manner. That is the cell does not divide in an uncontrolled manner, if that occurs then it leads to cancer. When cancer occurs, the cell division is continuous, and the newly formed cells stay attached to one another . Thus leading to tumor growth.

Types of cancer immunotherapy

Different types of cancer immunotherapies.

Immune checkpoint inhibitor

What are immune checkpoints?

A very characteristic feature of the immune cell is its ability to differentiate our body cells from foreign particles. The proteins present on the surface of the immune cells called the checkpoint proteins help in this feature of the immune system. The activation or deactivation of these checkpoint proteins helps to activate our immunity system . In the case of cancer, the cells with cancer evade these checkpoint inhibitors, thereby escaping our immune system.

What are checkpoint inhibitors?

Monoclonal antibodies produced against the checkpoint proteins are Checkpoint inhibitors. In general, the body produces polyclonal antibodies. These, polyclonal antibodies have affinity for different antigens (proteins) present on the surface of the organisms. The checkpoint inhibitors bind to the checkpoint proteins and prevent them from functioning properly. Checkpoint inhibitors are administered intravenous infusions. Some of the checkpoint inhibitors are :

PD-1 and PD-L1 inhibitors

The PD1 or programmed cell death protein 1 are special types of proteins present on the surface of the activated T cells of the immune system. The PD-L1, programmed cell death ligand 1 are present on the surface of normal cells and some of the cancer cells. The binding of PD1 to PD-L1 prevents the action of the T cells. The T cells do not recogonise the cells with PD-L1 as foreign. Thus our body does not mount an immune response against these cells. Some cancer cells have PD-L1 proteins in large numbers. So they evade the immune system. Some of the PD1 inhibitors are pembrolizumab, nivolumab, etc. Atezolizumab, avelumab, etc. are some of the inhibitors of the PD-L1 protein.

CTLA- 4 inhibitors

CTLA- 4 is a protein present on the surface of some of the T cells. They help keep the immune system under check. Ipilimumab and tremelimumab are some of the CTLA4 inhibitors. They bind the CTLA-4 proteins on T cells and block the protein, thus, preventing the proper functioning of these proteins. These CTLA -4 inhibitors are administered in combination with PD-1 and PD-L1 inhibitors.

LAG-3 inhibitor

The LAG-3 inhibitors are present on the surface of T cells and help keep the immune system under check. The LAG-3 inhibitors like relatlimab bind to these proteins, preventing their proper functioning. The LAG inhibitors PD1 and PD-L1 are administered in combination therapy.

Side effects of checkpoint inhibitors

There can be some common side effects, like nausea, constipation, fatigue, and muscle pain. In some patients, infusion reactions can occur. Autoimmune disease is one of the serious side effects of checkpoint inhibitors. Autoimmune condition occurs due to the uncontrolled immune response caused due to the blocking of the checkpoint proteins. It is necessary to bring this instance to the doctor’s attention.

Adoptive cell transfer

The patient’s immune cells are used in adoptive cell transfer to stimulate a strong immune response. T cells are extracted from the patient’s peripheral blood or tumor cells. While T cells from peripheral blood must be stimulated to become tumor-specific, T cells extracted from tumors are unique to the cancer. These T cells are then let to proliferate in the laboratory. After then, the patient is administered with these cells, which cause the tumor to become immune-mediated and eventually die.

CAR-T cell therapy

In this therapy the patient’s T- cells are collected from the blood. Then the cells are then genetically modified to identify certain proteins on the surface of the cancer cells called the chimeric proteins. These genetically modified T cells are called CAR-T cells ( Chimeric T-cells ). They are administered to the patient intravenously. Before the infusion is administered, the person receives treatment to suppress their immune system. These CAR-T cells are specific to each cancer, as the chimeric protein differs. It is one of the most effective types of treatment of cancer. Some of the approved CAR-T cell therapies are Kymriah, Tecartus, Abecma, etc. Some of the side effects of CAR-T are the release of large amounts of cytokines, a condition called cytokine release syndrome, nervous system problems, infusion reactions, low immunity, and low blood count.

Cancer vaccine

In some cases, infection with certain viruses can cause cancer. Like in the case of human papillomavirus, which is related to cervical, vulval, vaginal, and some throat cancer. In these cases the vaccines used against these viruses can prevent the occurrence of these cancers. In general, the vaccine against cancer will not prevent it but it will help the body fight cancer. Mostly, vaccines for cancer are prepared from the antigen or the tumor cells . When administered ,it will trigger our body to elicit an immune response against the cancer. Proveng, used to treat prostate cancer, and T-VEC, used to treat melanoma skin cancer, are some of the cancer vaccines.

Monoclonal Antibodies

Monoclonal antibodies are synthetically produced in laboratories with specificity to a particular antigen. These antibodies structurally resemble the naturally produced antibodies in the human body. In cancer immunotherapy employs three types of monoclonal antibodies.

Naked monoclonal antibodies

These antibodies are naked or without any attachment. They are specific for either a protein on the surface of the cancer cells or the checkpoint proteins on the T cells. The monoclonal antibodies against cancer proteins bind to the protein on cancer cells and make it a target for the immune cells. In some cases, the monoclonal antibodies bind to certain proteins called blocking proteins on the surface of cancer cells, thereby preventing the growth and spread of the cancer cells.

Conjugated monoclonal antibodies

Conjugated monoclonal antibodies are antibodies with either a drug or radioactive material attached to it. When they attach to the cancer cell, they deliver the drug or the radioactive agent directly to these cells. Thereby leading to cancer cell death.

Bispecific monoclonal antibodies

These monoclonal antibodies have specificity for two proteins; they can bind to a protein on the surface of the cancer cell and, at the same time, bind to a protein on the surface of a T-cell, thereby bringing these cells together. Thereby causing the destruction of the cancer cells. Some of the examples of monoclonal antibodies are rituxan, herceptin, adcetris, kadcyla, etc.

Oncolytic virus therapy

Oncolytic viruses are viruses that have been altered especially to target cancer cells. They have been specially altered to attack tumor cells rather than healthy cells. These viruses stimulate the production of an immune activator that attacks the tumor cells once they have taken over the tumor cell. The virus may occasionally carry certain medicinal substances. These viruses have the ability to lyse tumor cells. Consequently, the antigens are released, causing the immune system to attack the cancer cells.

Conclusion

There are many immunotherapies available for cancer, and in time to come, there will be even more research in this field to ensure more options are available. Compared to chemotherapy and radiation, immunotherapies are effective and safe.