Immunotherapy is a new treatment approach for cancer. Immunotherapy seeks to harness the power of the immune system to combat and control cancer. Immunotherapy joins chemotherapy, radiation, surgery and targeted therapies as the newest recognized class of anti-tumor treatment.
The immune system helps your body fight infections and other diseases. It is made up of white blood cells and organs and tissues of the lymph system. Immunotherapy is a type of biological therapy. Biological therapies are treatments which are contain, or are derived from, living cells.
The major categories of immunotherapy are: (1) monoclonal antibodies (including checkpoint blockade); (2) cytokines; (3) adoptive cell transfer; and (4) therapeutic vaccines.
Currently, no immunotherapy has demonstrated effectiveness in metastatic colorectal cancer. This clinical trial is evaluating a therapeutic vaccine type of immunotherapy.
The following is a brief description of these different types of immunotherapy:
Monoclonal Antibodies (mAbs) are a special type of protein designed to target antigens, or markers, located on the surface of cancer cells or on cells which influence the cancer cells. These mAbs can locate antigens and subsequently recruit immune cells to attack the cells that express the targeted antigens. mAbs can also interfere with cell signaling, helping to block growth and communication of tumor cells.
- Immunotherapy mAbs are approved by the FDA for a wide range of cancers including:
- Breast (Herceptin®, Kadcyla®, Perjeta®)
- Hodgkin’s lymphoma (Adcetris®)
- Non-Hodgkin’s lymphoma (Rituxan®, Zevalin®)
- Colorectal (Avastin®, Erbitux®, Vectibix®)
- Lung (Avastin®, Cyramza®)
- Chronic lymphocytic leukemia (Gazyva®, Campath®, Rituxan®, Arzerra®)
- Gastric (Herceptin®, Cyramza®)
- Kidney (Avastin®)
- Brain (Avastin®)
- Cervical (Avastin®)
- Ovarian (Avastin®)
- Acute lymphoblastic leukemia (Blincyto®)
The latest versions of mAb immunotherapy is a class of mAbs referred to as “Checkpoint Blockade”. Checkpoint molecules are expressed on some tumor cells as a means to avoid immune cell destruction. When these checkpoint molecules are blocked using a mAb, they “release the breaks” on an existing immune response that was previously suppressed.
Yervoy® (ipilimumab) was the first checkpoint blockade drug approved by the FDA for the treatment of melanoma. Subsequently, Yervoy also obtained approval for the treatment of non-small cell lung cancer and prostate cancer. Yervoy blocks the checkpoint molecule known as CTLA-4.
Keytruda® and Opdivo® are also currently approved by the FDA for the treatment of melanoma after failing prior treatment with Yervoy®. These drugs block the checkpoint molecules known as PD-1 or PD-L1.
Many clinical trials are in progress with other checkpoint targets (such as LAG-3 and KIR). In addition, approved checkpoint blockade drugs are being tested in different cancer indications and in combination with other treatments (both approved and experimental).
Currently, the evidence suggests that this class of immunotherapy is not effective in metastatic colorectal cancer.
Cytokines are proteins that are made by your body’s cells. These proteins play a role in the delivering signals to immune cells, and cells which interact with immune cells,which control their function. Cytokines play an important role in the body’s normal immune responses and also in the immune system’s ability to respond to cancer.
Examples of cytokines are: interferons (such as interferon-alpha) and interleukins (such as IL-2). This class of immunotherapy also has not demonstrated efficacy in metastatic colorectal cancer.
Currently, cytokines have not found to be effective in metastatic colorectal cancer.
Adoptive cell transfer
Adoptive cell transfer (ACT) is a treatment that attempts to boost the natural ability of immune cells to fight cancer. These procedures will remove blood or tissue from a patient and then isolate a type of immune cell (such as T-cells or NK cells) from the blood or tissue in the laboratory. The isolated immune cells are then grown to large numbers and/or the genes are modified in the immune cells in an effort to make them better able to find and destroy cancer cells. These immune cells that have been expanded and/or modified outside the body are then infused back to the patient donor via a needle in a vein as therapy. Some adoptive cell therapy protocols also require some form of chemotherapy prior to the infusion of immune cells in order to weaken the resident immune response so the newly infused immune cells can dominate.
Examples of this type of immune therapy: Dendritic cell, LAK, NK, CAR-T, KIR and tumorspecific CTL (killer cells). There are several experimental adoptive immunotherapy protocols under investigation for metastatic colorectal cancer.
Therapeutic vaccines are treatments for existing disease, whereas prophylactic vaccines are designed to prevent disease occurrence. Therapeutic cancer vaccines are methods designed to educate the immune system to identify and then eliminate cancer cells whereever they are found throughout the body. If effectively designed, these experimental treatments are able to elicit a “memory” immune response. This unique feature of therapeutic vaccines would enable an effective protective immune response to re-emerge without further treatment, upon the recurrence of a tumor.
While there have been many attempts at developing therapeutic cancer vaccines for metastatic cancer, this has been found to be a very challenging area of research. Most therapeutic vaccines have demonstrated poor results in the clinic.
To learn more about the therapeutic vaccine under investigation in this clinical trial and the unique features of this experimental approach that led investigators to believe that this vaccine might succeed where others have failed is available under the Experimental Vaccine tab.