Chimeric antigen receptor (CAR) T-cell therapy is emerging as an effective therapeutic strategy for patients with B-cell lymphoid cancers. Over the last five years, it has been used for patients with relapsed diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Recently, CAR T therapy was approved by the FDA to treat patients with relapsed/refractory chronic lymphocytic leukemia (CLL). With currently available CAR T therapy products, long-term cancer control can be observed in around 40% of patients. There is a need to develop better forms of CAR T therapies to maximize their potential.
"Armored" CART-cells are a new generation of CAR T products that are being evaluated in clinical trials. Roswell Park Comprehensive Cancer Center is conducting a first-in-human Phase I trial of CD19-Targeted Chimeric Antigen Receptor Modified T Cells Genetically Engineered to Secrete Interleukin 12 (IL-12 ). This enhanced form of immunotherapy was developed by Roswell Park scientists in collaboration with scientists at Memorial Sloan Kettering.
The T cells used in this trial will be manufactured at Roswell Park's expanded state-of-the-art GMP Engineering & Cell Manufacturing Facility for the first time. "We will have the infrastructure, the process, the support structure to not only manufacture cells for therapy but also to be able to support a clinical trial and have the resources in place to be able to infuse these therapies into a patient,” says Christopher Choi, PhD, MBA Senior Vice President of Industry Partnerships and Technical Director of GMP Facility at Roswell Park.
I'm Doctor Francisco Hernandez Eliza to I'm the Director of the lymphoma Research Program at Rossell Park Comprehensive Cancer Center. We're excited to kind of reach out to you guys to talk about our phase one clinical trial, looking at an armored car who secrets um Ielt uh 12 or into looking 12 TC 19 BLM that will be in charge of taking care of the patients, treating the patients, monitoring the side effects and certainly monitoring the integrity of the story. By reporting an even over the last two decades, we have evolved from using what we call monoclonal antibodies, tin receptors in cancer cells to actually integrate in drugs that are able to enhance the immune effector cells like natural killer cells. American T receptor therapy. It is a technology that allows to reengineer the T cells of the patients to give them tools to recognize a receptor present in the cancer cells and to activate themselves to expand and to kill the cancer cells. Cardi therapy is approved to treat patients with raps, frac large B cell lymphoma, patients with a las fracture follicle lymphoma, ch leukemia and manto cell lymphoma. While 40% of the patients tend to do well with this therapy, there's still 60% of the patients who unfortunately uh the cancer comes back because the card T cells do not stay living longer or the cancer cells develop some forms of resistance. So that's a kind of in somehow stimulated scientists across the world to try to develop a new generation of cars T cells. They are now known as armored car T cells, meaning that these are kind of a further step in the development of this therapeutic platform in which uh car cells are not only in engineer to recognize the cancer to activate it and to kill the cancer, but I also re engineered to secrete uh cytokines that would allow these T cells to enhance better, to recruit other immune cells into the tumor bed and to hopefully kill the cancer better and lead to better results in terms of outcomes for patients with a fracture lymphoma. When we're looking at these new armored cars, you know, particularly the one that we're gonna be testing at R Park Cancer Institute. The T cells will be engineered initially with our collaborators Malo Cat Hospital, but the B that will be actually performed at Rosso Park Council Institute, one of our core facilities that will be lead by Dr Choi. Hi, I'm Chris Choi. I'm the SVP of industry partnerships and the technical director of the GMP facility here at Roswell Park. What really makes us unique versus a CD mo that you would find somewhere else is we're going to have what we believe is the largest academic GMP facility in the country. So in terms of capacity, if you have an idea and you want to do a trial and you want GMP manufacturing, we have the capacity to do that. But really if you have an idea, the fact that we can take that idea and do the preclinical work that's necessary for the eventual first in human IND and then also do the GMP work, meaning that if you have a research project, how do you actually make that? So it can be put into humans? And that's what we call good manufacture during practices. And how do you do that process development? So my team's really in charge of doing that and once we have that process in place and the manufacturing of the viral vector and all the other critical components and drug substances, then what we can do is work with the CRS work with the clinical team, the nurses, the administrative group and get that into first and human. We're leveraging a lot of the DNA and capabilities already here at Roswell Park. Our group really will be involved from end to end for this clinical trial in general. We're looking for patients who they have relapse refractory piece of malignancies. So they have progressed after at least two problems of treatments, there are side effects that they may happen within the 1st 2 to 4 weeks after the cardi therapy infusion and they had to do with activation of the immune system that can lead to an inflammatory response that can actually be perceived as a sepsis. In addition to that car therapy can produce what we call neurotoxicity. We do not know the basis for that. The severity of the neurotoxicity is very rare for the most part patients. They have no neurotoxicity or they have mild headaches or a little bit of problems. Finding words, general toxicity is reversible and no responds well to steroids. We're hoping to see um in this particular clinical trial, administering an armored car that is able to create uh interleukin 12 is gonna be safe. It's not gonna have too much side effects compared to commercial cars. It's also gonna show that it's active, you know, even in patients that they have prior commercial card therapy that I want to see if maybe this therapy will result in more patients staying in remission longer, you have a patient that has a relapse of fracture, uh VSA lymphoma that you think may benefit from this treatment. And it's interesting to come here and spend a day with us, uh you know, feel, feel free to reach out to us. Any questions that you have about the story. Um You know, we're very happy to, to talk to you and answer any kind of questions or concerns
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