VIRAL IMMUNOTHERAPY

WHAT IS IMMUNOTHERAPY?

Learn about the side effects of the treatment of cancers and how viral immunotherapy could help.

BACKGROUND

"Stem cell and organ transplantation are considered as the major advances of modern medicine. Unfortunately the success of transplantation is limited by its toxicity and infectious complications as a result of profound immunosuppression. Viral infections are an extremely common and predictable problem in these patients. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. Over the last few years, there is increasing evidence that cellular immune therapies can reverse the outgrowth of haematological malignancies and can also provide therapeutic benefit against lethal viral infections. While the expansion and adoptive transfer of virus-specific T-cells from the healthy donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Recent studies have demonstrated successful expansion of virus-specific T-cells from seropositive stem cell transplant recipients of a seronegative graft with active virus disease and the long term reconstitution of protective anti-viral immunity following their adoptive transfer back into the patients. Furthermore, this immunotherapeutic strategy has also been extended for multiple pathogens including cytomegalovirus, Epstein-Barr virus, adenovirus and BK polyoma-virus. This approach can be employed to rapidly expand multiple pathogens-specific T cells that can be used for adoptive immunotherapy. Finally, new assays to monitor T cell immunity have been developed which will allow to identify the high risk transplant patients who may develop virus-associated complications post-transplantation and can be given adoptive T cell therapy prophylactically."

TYPES OF IMMUNOTHERAPY

"Several types of immunotherapy are used to treat cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Types of immunotherapy that help the immune system act directly against the cancer include:

Checkpoint inhibitors, which are drugs that help the immune system respond more strongly to a tumor. These drugs work by releasing “brakes” that keep T cells (a type of white blood cell and part of the immune system) from killing cancer cells. These drugs do not target the tumor directly. Instead, they interfere with the ability of cancer cells to avoid immune system attack.
Adoptive cell transfer, which is a treatment that attempts to boost the natural ability of your T cells to fight cancer. In this treatment, T cells are taken from your tumor. Then those that are most active against your cancer are grown in large batches in the lab.

The process of growing your T cells in the lab can take 2 to 8 weeks. During this time, you may have treatments such as chemotherapy and radiation therapy to reduce your immune cells. After these treatments, the T cells that were grown in the lab will be given back to you via a needle in your vein.

For more information about a specific type of adoptive cell transfer called CAR T-cell therapy, which uses T cells that are changed in the laboratory, see CAR T-Cell Therapy: Engineering Patients' Immune Cells to Treat Their Cancers.
Monoclonal antibodies, also known as therapeutic antibodies, are immune system proteins produced in the lab. These antibodies are designed to attach to specific targets found on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system, and these are a type of immunotherapy. Other monoclonal antibodies that are used in cancer treatment do not cause a response from the immune system. Such monoclonal antibodies are considered to be targeted therapy, rather than immunotherapy.

Learn more about targeted therapy.
Treatment vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.

Types of immunotherapy that enhance the body’s immune response to fight the cancer include:

Cytokines, which are proteins made by your body’s cells. They play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons and interleukins.

BCG, which stands for Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacteria that causes tuberculosis. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer."

T-CELLS

"As its name implies, the backbone of CAR T-cell therapy is T cells, which are often called the workhorses of the immune system because of their critical role in orchestrating the immune response and killing cells infected by pathogens. The therapy requires drawing blood from patients and separating out the T cells. Next, using a disarmed virus, the T cells are genetically engineered to produce receptors on their surface called chimeric antigen receptors, or CARs.

These receptors are “synthetic molecules, they don’t exist naturally,” explained Carl June, M.D., of the University of Pennsylvania Abramson Cancer Center, during a recent presentation on CAR T cells at the National Institutes of Health campus. Dr. June has led a series of CAR T cell clinical trials, largely in patients with leukemia.

These special receptors allow the T cells to recognize and attach to a specific protein, or antigen, on tumor cells. The CAR T cell therapies furthest along in development target an antigen found on B cells called CD19 (see “The Making of a CAR T Cell”).

Once the collected T cells have been engineered to express the antigen-specific CAR, they are “expanded” in the laboratory into the hundreds of millions.

The final step is the infusion of the CAR T cells into the patient (which is preceded by a “lymphodepleting” chemotherapy regimen). If all goes as planned, the engineered cells further multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces."

Immunotherapy boosts the body’s defense towards cancer by using substances, made in the body or in the laboratory, such as:

Made in laboratories can be used in various ways, one of which is to use target therapy to block abnormal protein in a cancer cell.

Monoclonal Antibodies and Tumor-Agnostic Therapies

Genetically modified viruses that is injected into a specific tumor where the viruses undergoes the lytic cycle, at the end of this cycle when the cell bursts and die releasing antigens which triggers the immune system to target the cancer cells that have the same antigens (important because this does not attack healthy cells, unlike chemotherapy which attacks all rapidly developing cells).

Oncolytic Virus

+ Chemotherapy and radiation therapy

+Interferons- helps aid the immune system to fight or slow the growth of cancer cells

+Interleukins- helps the immune system produce cells to kill the cancer

Non-Specific Immunotherapies

T-cells are removed from a patient's blood and is altered in the laboratory to have receptors, specific proteins, that allows the T- cells to recognize and destroy the cancer cells

T- Cell therapy

These cancer vaccines allows the body to be exposed to antigens that recognizes and destroys the cancer cell.

There are two types: prevention vaccines and treatment vaccines.

Virotherapy