The original research performed at the Institute was focused on elucidating the relationship between herpes virus (Epstein Barr virus and Marek’s disease virus) infections and the development of cancer. Then, with the emergence of the AIDS outbreak, the Institute's research program was expanded to include investigations of the human immunodeficiency virus (HIV), and the development of vaccines and therapeutics to prevent or eliminate HIV infections.
As the studies of EBV, MDV, and HIV continued it became clear that these viruses acted much differently in the test tube than they did in the body. All three of these viruses were found to infect key cells of the immune system - EBV was found to infect B lymphocytes, MDV was found to infect monocytes and T lymphocytes, while HIV was found to infect T lymphocytes and numerous other critical immune cells. While the viruses could infect these same cells in the test tube, the diseases that these viruses induced could not be replicated in the test tube. As it turns out, the monocytes, and B and T lymphocytes are key components of the immune system and infection of these cells in the body significantly alters how these cells, and subsequently, how the immune system reacts. This cannot be replicated in the test tube. Therefore, in order to understand how these viruses create disease, and how best to control them, we must understand how they interact with the immune system.
Interestingly, the same can be said for cancer and a myriad of other diseases. Recent cancer studies have found that cancer cells can secrete factors that block the immune system from attacking them. If this immune suppression can be overcome, the immune system can attack and even completely eliminate the cancer. Likewise, reversing the immune suppression induced by viruses and other infectious agents, or suppressing the abnormal immune responses associated with autoimmune diseases and allergies and asthma, can significantly improve recovery from these conditions.
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Immunotherapy relies on the body’s own immune system to fight disease. The idea for immune therapy goes back to the late 19th century when Dr. William Coley injected bacteria into tumors and saw the tumors shrink. It was eventually discovered that the tumor cells were being killed by an immune response provoked by the injected bacteria. This suggests that the immune system has the power, when properly stimulated, to attack and even eliminate a growing cancer. However, due to the tremendous complexity of the immune system, scientists struggled for decades to turn Dr. Coley’s observations into effective cancer treatments. It’s only been recently that therapies based on modulating the immune system (other than vaccines) have made it into the clinic. Even with the initial limited success of immunotherapies there are now high expectations that immunotherapy will provide the next great breakthroughs in cancer treatment.
As stated by Max S. Wicha, director of the University of Michigan Cancer Center, “After years of research, we are now, for the first time, moving beyond the traditional cancer therapies of chemotherapy, radiation and surgery. One of the approaches we are most excited about is immunotherapy, because it is based on a fundamental knowledge of how the human immune system works and recognizes cancers to destroy them. It also fits in with other therapies of the future, which will use genetics and molecular biology to target cancers in a much more specific way."
Immunotherapy offers great promise as a new tool for the treatment of cancer and many other diseases. Recent advances in our understanding of tumor immunology have greatly expanded the potential applicability of this therapeutic approach, with benefits now being seen in patients with tumor types not previously thought to be amenable to such treatment. These include patients with prostate, lung and brain cancers as well as a variety of hematologic malignancies, who have benefited from immunotherapy, either used alone or in combination with chemotherapy, radiation or surgery. Within the last few years, two cancer immunotherapy approaches have been approved by the FDA: Provenge® (Sipuleucel-T) for castration-resistant prostate cancer and YERVOY™ (anti-CTLA-4 monoclonal antibody) for patients with advanced stages of melanoma.
Further, exciting advances are on the horizon with opportunities to develop combinations of either active immunotherapies or an immunotherapy together or with novel molecularly targeted therapies, which raise the potential for prolongation of survival in a large percentage of patients whose diseases were previously felt to be incurable.
According to Lloyd J. Old, MD, Director of the Cancer Vaccine Collaborative affiliated with the Ludwig Institute for Cancer Research, the three key questions that are critical to developing more effective immune-based treatments include the following.
1. How does the immune system recognize cancer?
2. What are the antigens that the immune system targets?
3. How can you strengthen the immune response?
How the Immune System Works
These are but a few of the questions the investigators at TBRI will be pursuing as their research continues to be focused on harnessing the power of the immune system to treat, cure and prevent cancer and debilitating diseases.