| 1 | HealthTree Foundation for Multiple Myeloma | What is translational research? | 5515 | 64 | 1 | 57.6 | positive | 2:21 | What is translational research? So translational research is the middle ground between basic science research, which is very basic fundamental biological research and clinical research, which is clinical trials when we test new therapies with patients. So translational research is a fairly broad field. It covers any sort of disease biology associated research. And that can be many things. It can be a laboratory model that you do in a dish, but it has many of the elements of the human disease. So in myeloma, you hear a lot about bone marrow stromal co-culture models. That sounds really complicated. But what it means is in a dish, we're trying to recreate the bone marrow microenvironment of myeloma. There's bone marrow cells such as stromal cells and stem cells and then myeloma cells so that you have kind of a recreation of the bone marrow microenvironment. So that's one example. A second example is an animal model. So you hear a lot about zina graft models or engineered animal models of myeloma. Sometimes you can take myeloma cells out of a patient and transplant them into a mouse and then treat those mice with drugs to see if they work in a living system. So that's another example of translational research. Or you can take cells out of a patient, the myeloma cells or other types of cells out of a patient and analyze them to see if you can identify genetic mutations, for example. So anything that touches on the actual disease, whether it's a laboratory model or experiments that you do with actual tumor cells from patients or other material from patients such as bone marrow, immune cells and so forth. These are all examples of translational research. Thanks for watching. By creating a health tree account, you can get exclusive access to the latest health tree university content, track your course progress, take quizzes and bookmark lessons, visit the links in the description below to get started. | ↗ |
| 2 | HealthTree Foundation for Multiple Myeloma | What are Immunomodulatory drugs (IMiDs) and how do they work? #myeloma | 9323 | 103 | 4 | 54.5 | positive | 5:49 | What are imits and how do they work? Imits are immunomolatory drugs. There are class of drugs that are based on the first drug called Tolidamide and was approved a while ago. Now there's a class of drugs that is based on the same structure of Tolidamide, Lennelolamide and together they form the class of imits or immunomolatory drugs. And these drugs are old drugs that are very important cornerstone of most of the regimens that we use to treat multiple myeloma both upfront as well as in later lines of disease. And over time by tweaking the structure of the drug we have been able to develop more powerful compounds generally. And so we know very well from studies in the past that imits have a direct effect on the tumor and they sort of result in cell death and prevent the proliferation of myeloma cells. But very importantly the fact why we call the immunomolatory is the fact that they don't just have their effect on myeloma cells but they act very importantly on cells that consist of the so-called immune microenvironment of multiple myeloma. In the bone marrow so where the tumor is growing there's a lot of other cells of the immune system as well and we believe that they contribute or they can contribute to tumor killing and imits have an important effect on the cells of the immune microenvironment. More specifically we know that they activate T cells and NK cells, natural killer cells and both of these cells are known to be able to exert an anti-tumor effect. And I think that is part of the power of the immunomolatory agents. These are immunomodulatory agents that have been used in the treatment of myeloma and have transformed them. The first drug was thlytomide and interestingly the mechanism of action of these drugs was unknown despite very significant clinical activity. It is now felt that the major action of these drugs is most likely through a combination of targeting the myeloma tumor cell itself but most importantly also the tumor environment. The targets that have been identified and electrically have been cereblon as well as some zinc finger proteins such as Icarus and Iolus that are present both in the myeloma cells as well as in T cells and other immune cells within the microenvironment. But how exactly these mechanisms affect everything is not really fully invested at this point. So imits of course have a slightly controversial history prior to the discovery that they were effective in myeloma thlytomide was as a lot of people know initially used for morning sickness and pregnant women and obviously that had a terrible to radigenic or birth defect effects. It was later actually realized that this compound could have a beneficial effect in myeloma and it was tested in that arena and had some efficacy. Myeloma also has some nerve toxicity and causes psalmolins so its next generation agents let me a little bit and pome a little bit have less of these neurologic side effects and are very effective and better tolerated as well. As a class of drugs these drugs target both the myeloma cell and also immune cells. What they do is they actually lead to the degradation of specific proteins they are called Icarose proteins and those proteins that are degraded actually affect different processes in the myeloma cells that leads to the death of the myeloma cells then in the immune cells. In the immune cells they actually lead to further activation of immune cells and so in that sense that's why they are called the immunomodulatory drugs because they have this multiple immune effects where they lead to activation of natural killer cells and T cells that are thought to be important in part of the efficacy of these drugs. Are imits considered a form of immunotherapy? They can potentially be considered a form of immunotherapy. I think one of the challenges of that is that they are not necessarily clearly directed at the myeloma. It's perhaps more of a non-specific immune activation. Some of it made me myeloma directed some of it may not be. That is not very well understood I think at this point. How do imits target the microenvironment? Targeting the microenvironment I think there's become a bigger appreciation for the fact that the way to eradicate myeloma is through direct killing of the tumor cell itself but also of inhibition of the immunosuppressive mechanisms that exist within the bone marrow and microenvironment and also activation of immune functions that exist within the bone marrow and microenvironment. So for example there are suppressive populations such as myeloid derived suppressor cells. Non-suppressive factors such as bed jab or interleukin six or potentially even IL-17 that are known to inhibit the ability of the immune system to effectively kill myeloma. These are most likely down-regulated by the use of imits and then there are T cells that are known to kill and able to kill myeloma that have been shown to be up-regulated and to be able to kill more effectively when given or when exposed to a variety of imits. Lannolidamide and pomellolidamide as well as the newer imits. | ↗ |
| 3 | HealthTree Foundation for Multiple Myeloma | What are immunomodulatory drugs (IMiDs) and how do they work? #myeloma | 4017 | 29 | 1 | 50.3 | | 2:53 | What are immunomodulatory drugs and how do they work? So, imids, of course, have a slightly controversial history prior to the discovery that they were effective in myeloma. Felidomide was, as a lot of people know, initially used for morning sickness in pregnant women. Obviously, that had terrible, teratogenic or birth defect effects. It was later actually realized that this compound could have a beneficial effect in myeloma and it was tested in that arena and had some efficacy. Felidomide also has some nerve toxicity and causes psalmolins. So its next generation agents, linolytomide and pomolytomide, have less of these neurologic side effects and are very effective and better tolerated as well. As a class of drugs, these drugs target both the myeloma cell and also immune cells. What they do is they actually lead to the degradation of specific proteins. They are called Icarose proteins. Those proteins that are degraded actually affect different processes in the myeloma cells that lead to the death of the myeloma cells. Then in the immune cells, in the immune cells, they actually lead to further activation of immune cells. In that sense, that's why they are called immunomodulatory drugs because they have this multiple immune effects where they lead to activation of natural killer cells and T-cells that are thought to be important in part of the efficacy of these drugs. So one form of immunotherapy that probably everybody is familiar with in very broad terms are drugs such as rebel mid and pomolytomide. These are developed as what are called immunomodulatory derivatives of a drug known as poliomide, which was a very old drug. What it does is that it globally improves the patient's immune system in addition to fighting the myeloma. So it probably has several roles. And that has really served as a baseline for a lot of other therapies that have been developed. The large part because it can't continue to modulate and potentially enhance immune responses. | ↗ |