I'm Tariq Mohideen. I'm a fourth year hematology oncology fellow at the Tisch Cancer Institute at Mount Sinai, New York. For the past year or two, I've been focusing on translational work, research work on immunotherapies in multiple myeloma. Specifically, I'm focused on patients receiving bispecific antibodies, and more specifically, a bispecific antibody telkeremab, which binds to GPRC5D, and that is one of the proteins expressed on myeloma cells. So the problem that we have, unfortunately, is that there are a lot of patients who do not respond to telkeremab or other bispecifics, or after they initially respond, they eventually relapse. So we believe that this can be due to several factors. It could be due to the cancer itself not being appropriately targeted by the bispecific, or it could be the patient's own immune system not being able to fight the cancer appropriately. And in order to try to improve responses, we believe that trying to help the immune system somehow might improve the outcomes for patients. So what we did was we looked at patients who received telkeremab on the Monumental One trial. That was the first trial for telkeremab. And those patients actually, a lot of them donated samples to us, peripheral blood and bone marrow, and those samples were taken from baseline and at different time points throughout treatment. And those samples basically have the patient's immune cells. What we did was we took the patient's immune cells and we put them in culture in the lab. So I used pipettes and pet tree dishes and flasks, and I incubated them with myeloma cells and I added the bispecific on top of them. And I saw how effective was the immune system's ability to kill myeloma cells and on the bench basically in the lab. And I noticed that throughout treatment, if I take samples from prior to therapy and throughout treatment, the effect or the ability of the immune system to fight the myeloma starts decreasing over time. So one way to improve that was to make the T cells, which are part of the immune system, stronger. And one way to do that is to block any signals they receive that could dampen their effect. So the signals that can decrease the effect or the ability of T cells can come from the cancer cells themselves. So myeloma cells express certain markers that when the T cells see them, they get dampened or suppressed and they're not able to kill the myeloma cells. One way of blocking those signals is using checkpoint inhibitors. So we have multiple checkpoint inhibitors available and so far most of them are being used in cancers that are from the solid cancer field. So something like lung cancer or gastric cancers or genitourinary cancers. So we have a lot of solid cancers that have shown efficacy with checkpoint inhibitors. So what I'm trying to show and see if that's the case is if I add those checkpoint inhibitors on patient specimens in the lab though, if that improves the T cells and their function. And interestingly, we were able to actually see an improvement in the immune system. So if I combine patients' immune cells with the myeloma cells and add on top of it the bispecific and the checkpoint inhibitors, the effect or the ability of the immune system or the T cells specifically become more augmented. So basically the ability to kill myeloma cells starts increasing. And that is very interesting data. And while it is still at the research level in the lab, we hope that maybe in the future we would be able to bring it to patients in the clinic and see if that actually also improves outcomes in the clinic. And for patients specifically who start on a bispecific and relapse within a few months, maybe by using checkpoint inhibitors, we'll be able to extend that response for many years. And that's definitely our hope. And that's been our research for the past couple of years.
HealthTree • January 13, 2025