Non-Specific Immunotherapy

Non-specific immunotherapy for mesothelioma and other cancers uses a substance that stimulates the overall immune system so that antibodies that fight foreign substances, like cancer cells, will be more effective in destroying them. These substances do not have to bind themselves to a specific antigen (foreign substances) to boost the immune response.

Originally, non-specific immunotherapy substances were studied for their ability to work alone as anti-tumor agents. However, the focus is on using them in combination with antigen-specific active immunotherapy.

Types of Non-Specific Immunotherapy

There are several general types of non-specific immunotherapeutic agents. They include:

• Cytokines
• Bacille Calmette-Guerin (BCG) Therapy
• Cell therapy

Cytokines

Cytokines such as tumor necrosis factor, interferon and interleukin-2, are used in active immunotherapy to cause cancer cells to die or to stop creating new cells. They interact directly with the tumor cells and are given individually or in combination to take advantage of the effect of all of them working together, which is more effective than what each can do individually.

Using cytokines non-specifically to boost the immune response includes:

• Interleukin-2 to stimulate the creation of T-cell and natural killer (NK) cells.
• Interferon to make antigen-presenting cells (cells that bring the antigen to the cell surface so it can be destroyed) more effective and increase the production of immune molecules like MHC, which help T-cells recognize antigen fragments.

Bacille Calmette-Guerin (BCG) Therapy

During1970s, researchers discovered that administering weakened forms of a mycobacterial strain called Bacille Calmette-Guerin (BCG) was effective in treating cancer. BCG is made from a live strain of tuberculosis virus found in oxen and cows.

A mycobacterium causes tuberculosis and leprosy. That is why BCG was originally made into a vaccine to treat tuberculosis, because it can help the body slowly develop immunity to the disease

It is not known exactly how BCG generates anticancer immune responses in some patients. The accepted theory is that it activates macrophages, white blood cells that surround an antigen, and then displays its fragments to activate T cells and lymphocytes, white blood cells that clone the proteins needed to fight specific antigens. In spite of its ability to stimulate production of these immune cells, BCG is only effective when given in combination with other therapies.

Researchers investigated the use of another mycobacterium called SRL172 in combination with multi-drug chemotherapy to treat non-small cell lung cancer and mesothelioma.

The concept underlying the research was that the administration of the chemotherapeutic agents would release either tumor-specific or tumor-associated antigens from the patient’s tumor and that the non-specific immune therapeutic agent SRL172 could simultaneously increase the effectiveness of the immune system to recognize specific antigens in patients whose immune system has been significantly weakened by the disease.

At the time of the study, all patients had symptoms such as a cough, shortness of breath and/or pain. After being injected with SRL172, the only adverse side effect the participants experienced was a thickening of the tissue around the injection site.

In the group treated with chemotherapy plus SRL172, the researchers found that:

• The average survival time was 9.4 months, compared to 7.5 months in the chemotherapy alone group.
• The response rate was54 percent, compared to 33 percent in the other group.
• And 42 percent of the patients were alive after one year, compared to 18 percent in the group receiving only chemotherapy.

Cell Therapy

Transferring live, whole cells into patients to achieve non-specific immunotherapy is a practice that researchers use on patients with advanced metastatic melanoma or renal cell carcinoma. It is also being investigated for use in patients with mesothelioma.

Human peripheral blood mononuclear cells (PBMCs) are cells that are round. They are also adept at fighting infections in the body.

When these white blood cells are boosted, they are more effective in destroying tumor cells. And when a combination of LAK cells and interleukin-2 are administered, tumor regression is experienced by about 10 percent of patients.