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Frequently Asked Questions About Therapeutic Antibodies

General Inquiries About Therapeutic Antibodies

• What is a therapeutic antibody?

  Therapeutic antibodies are laboratory-engineered substances that recognize and bind onto a protein on the surface of a cell. Each therapeutic antibody recognizes a different protein, or antigen, and in general can be used alone, in combination with chemotherapy or as a carrier of substances such as toxins or radiation. After binding to the targeted site, the therapeutic antibody can block the growth of the tumor and/or recruit the body's immune system to attack the target, and can also sensitize a cancer cell to chemotherapy.

• What is the difference between a murine, chimeric and humanized therapeutic antibody?

  A murine antibody is derived solely from mouse sequences and therefore is viewed as foreign by the host body and can elicit an antibody reaction on its own and be eliminated before having an effect. A chimeric antibody is a mixture of both mouse and human sequences, usually a 30/70 percent split, respectively, where the mouse components are responsible for binding to the antigen and the human components are involved in inducing a therapeutic effect. Humanized means the antibody contains over 90 percent human sequences.

• What does it mean when a therapeutic antibody is referred to as 'naked' or 'unlabeled'?

  The term 'naked' or 'unlabeled' is used when a therapeutic antibody is not a carrier of substances such as toxins or radiation. Sometimes naked or unlabeled antibodies are used because they attach themselves to specific antigens on cancer cells, marking the cancer cell for destruction by the immune system. Other naked or unlabeled therapeutic antibodies are used because they attach to certain sites, called receptors, on cancer cells where they signal cancer cells to die (apoptosis) or they can work by blocking other molecules that stimulate the cancer cells' growth from binding to the cancer cell. Blocking the other molecules from attaching there is how therapeutic antibodies prevent rapid growth of the cancer cells. Naked or unlabeled antibodies also can be used with other therapies such as chemotherapy.

Methods of Therapeutic Antibody Treatment

• What is retreatment?

  In cancer therapy, where patients are susceptible to relapse, it is common for patients to be treated several times during the course of their disease. Retreatment refers to the administration of the same therapy more than once for a patient's disease. Patients are unlikely to be retreated with the same chemotherapy due to cumulative toxicity or resistance. However, patients have been successfully retreated with chimeric and humanized therapeutic antibodies. Retreatment is less likely to be successful with murine antibodies because of the higher likelihood of developing an immune response (HAMA) when receiving the mouse antibody, for the second time.

• What is maintenance therapy and how does it differ from retreatment?

  Maintenance therapy is treatment that is given to extend a patient's response. In cancer, it can mean regular doses of an anticancer therapy, designed to maintain a patient in a remission (a stable condition), improve his/her response, prevent a future relapse or spreading of the tumor to other areas of the body. There are no definitive guidelines on the time frame to receive maintenance therapies.

• What are the main differences between how patients respond to therapeutic antibodies as compared to chemotherapy?

  Targeted therapies like therapeutic antibodies mainly affect specific cells since they attach to a particular antigen on the surface of the cell, most often malignant cells. While chemotherapy not only causes injury or death to the cancer cells, it also affects three other types of cells in the body that depend on the rapid growth of new cells to perform their normal function -- the lining of the gastrointestinal tract, the skin and scalp (hair follicles), and the bone marrow. The toxicity of chemotherapy and radiation therapy are cumulative and may lead to long-term toxicities and other types of cancers. Adverse events associated with therapeutic antibody therapy are most often infusion-related and can include chills, flu-like fever and respiratory events. Most of the adverse events are reversible with medical intervention, but severe and fatal events have occurred. Additionally, while chemotherapy regimens tend to have immediate effects on cancer and normal cells, responses to therapeutic antibodies can be ongoing or prolonged due to the long half-lives of many antibodies and ongoing treatment, and it can be several months before the final effectiveness is assessed.

• What does time to disease progression mean?

  This term refers to the length of time between when a patient first begins therapy of a cancer treatment and a subsequent relapse (additional spreading or growing of the cancer).

Non-Hodgkin's Lymphoma Specific Inquiries

• What are B-cells?

  The major cells of the immune system are white blood cells, which generally are comprised of macrophages, neutrophils and lymphocytes (B-lymphocytes, T-lymphocytes and natural killer cells). B-cells (B-lymphocytes) originate in the bone marrow and mature into plasma cells that secrete antibodies, the proteins that recognize and attach to foreign substances known as antigens. B-cells play a key role in the development of certain forms of cancer and autoimmune disorders.

• Why is duration of response important in evaluating non-Hodgkin's lymphoma treatments?

  During the natural course of indolent non-Hodgkin's lymphoma, patients will average five to six treatments during their lifetime. Because patients with indolent non-Hodgkin's lymphoma will ultimately relapse, the goal for a physician is to keep patients off therapy and free of relapse for as long as possible. Therefore, the most important endpoint in treating indolent non-Hodgkin's lymphoma is duration of response, as compared to response rate. Duration of response is a measure of the actual time that a patient responds to therapy and will be free of subsequent treatment, while the response rate is a single point-in-time measurement of a patient's CT scan to show how much tumor shrinkage occurred. To further illustrate this point, one patient can have a clear CT scan, a complete response, but have a duration of that response for six months, while another patient could have only a partial response to a therapy (i.e. cancer is visible on a CT scan) but that response could last a full year. Thus, the second patient would be off therapy for a longer period of time due to the durability of the response.

• What is radioimmunotherapy?

  Radioimmunotherapy is a combination therapy approach to treating cancer that currently combines the use of a murine therapeutic antibody that acts as a carrier vehicle delivering a radioisotope (radiation) to its intended target.