Passive Immunotherapy

Passive immunotherapy is a form of mesothelioma cancer therapy using substances that have been activated in vitro – outside the body (in a laboratory) – before their injection. It is also known as adoptive immunotherapy. This is contrasted to immunotherapy that is designed to stimulate the immune system through direct injection of antigens.

Passive immunotherapy is the giving of active immunity to a disease or virus to another someone. It is different from active immunotherapy, in which a human body's immune system is stimulated to fight off cancer cells.

History and Types of Passive Immunotherapy

Passive immunotherapy is hardly a new development in medical science. In fact, just the opposite. Animal- and human-born blood and serums were how patients with serious diseases were treated before the development of pharmaceuticals in the 1950s.

Passive immunotherapy can be accomplished in one of several ways, including naturally or artificially. Naturally acquired immunity comes from one person to another. For instance, a mother can pass along immunity to an unborn child through maternal antibodies.

Artificially acquired immunity means immunity by the addition of antibodies. These can be gained through a blood transfusion, by an injection or through IV fluids. Unlike naturally acquired immunity, artificially acquired immunity is not a long-term immunity.

There are two primary types of passive immunotherapy: monoclonal antibody therapy and antigen-loaded DC-based vaccines.

Monoclonal Antibody Therapy (mAb)

Monoclonal antibody therapy (mAb) is the most commonly used form of cancer immunotherapy. It is considered a targeted therapy because it is focused on a single site within the cancer cell, either an antigen on the surface of the cell or an enzyme or protein within the cell.

Monoclonal antibodies are ones are produced synthetically in a laboratory by the cloning of a single cell line. Monoclonal antibodies have identical antibody molecules as the antibodies from which they were cloned.

These monoclonal antibodies target only specific antigens on the surface of a mesothelioma cancer cell. When the antibody recognizes the antigen it normally fights, it sets off a chain reaction that ends with the death of the tumor cell. Monoclonal antibodies usually do not need the immune system to destroy cancer cells.

However, there are limitations to monoclonal antibodies. Among them:

• Their effectiveness is diminished because they are not used as first-line therapy. Typically, this type of therapy is used after the patient has already undergone surgery,chemotherapy and/or radiation therapy, and none of the treatments were a success. The toll these therapies have taken on the body may limit the ability of the mAb therapy to work.
• Not every patient may have the antigen against which the mAb therapy is directed. Although two patients may have mesothelioma, both patients do not necessarily have all the antigens associated with the disease. The success rate for targeted therapies is judged at 20 to 30 percent.
• Patients who undertook chemotherapy or radiation therapy may have tumor cells that have mutated. That alters the antigen on the cell surface at which the mAb therapy is directed. If the antigen is altered, the monoclonal antibody will not recognize it.
• Finally, a high level of toxicity is associated with this kind of therapy.

Antigen-loaded DC-based vaccines

Researchers continue to study active immunotherapy involving dendritic cells (DCs) as carriers for antigen targets. One serious drawback to this therapy is its reliance on identifying and characterizing the epitopes of antigens, or the part of the antigen that is recognized by the antibody that normally fights it. Only a small number of tumor-associated antigens for pleural mesothelioma have been defined.

Researchers investigated another tumor-associated antigen delivery based on the uptake of dead cells by immature dendritic cells. It involved creating a vaccine in the laboratory (in vitro) using HLA-A2+ dendritic cells from healthy donors and combining them with dead HLA-A2– mesothelioma cells either lacking or expressing heat shock protein 70 according to whether the tumor cells were heat shocked before they were killed with ultraviolet light. They found that the dendritic cells loaded with heat shock protein 70 cells were more effective in vitro stimulators of T lymphocyte activity against HLA-A2+ mesothelioma cells.

The benefit of developing an efficient in vitro vaccine instead of relying on a vaccine with a single or only a few identified antigens is that the in vitro vaccine rapidly gains access to two pathways, one that generates a response from T lymphocytes and one that generates a response from CD4+ T cells. This creates a diversified approach to destroying the cancer cells.