Project Term
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Project Summary
T cell cancers together comprise ~20% of acute leukemias and non-Hodgkin's lymphomas. A major challenge with currently available treatments for these is that the treatments themselves can damage or inhibit many of the patients healthy T cells that fight the cancer and prevent infections. Our strategy is to develop more personalized treatments that are better matched to each patient’s T cell cancer, improving efficacy and decreasing side effects.
Lay Abstract
T cell cancers are a clinically and biologically diverse group of leukemias and non-Hodgkin's lymphomas. There are many different forms including some of the most aggressive types, and together they make up about 20% of lymphocytic leukemias and lymphomas. Even though there are many different types, the cancerous T cells almost always have on their surface a unique receptor that can serve as a very specific target for treatment. Several therapies targeting the more common cell surface markers or growth of malignant T cells have proceeded to clinical trials, but these approaches must contend with risks of immune suppression since these treatments may also inhibit or kill a substantial portion of normal T cells that are so critical to fighting cancer and protecting against infections. Therefore, a major need exists for new strategies in the treatment of T cell leukemias and lymphomas where therapeutic agents exhibit high specificity and efficacy in the elimination of cancerous T cells with minimal effects on normal T cells. Our research program is designed to target patient-matched T cell receptors that identify a patient’s malignant T cells, while only also represented on a small fraction of the normal T cells. Having generated the code for many candidate new therapeutic agents and established a pipeline for testing them across the different types of T cell leukemias and lymphomas, we will now accelerate the development of a full panel of off-the-shelf agents will collectively enable the personalized treatment of the majority of patients with any type of T cell leukemia or lymphoma. We have already shown our capacity to generate such an effective patient-matched agent using multiple preclinical models of T cell lymphoma. To improve the effectiveness and persistence of these new therapies, we generate both therapeutic antibody and antibody-drug conjugate forms. Importantly, T cell leukemia and lymphoma cells persistently express these patient-matched receptors even after failing other treatments, and our strategy will personally match the treatment to each patient to improve patient outcomes and safety. In summary, our research to develop personalized therapies may allow us to treat matched patients with any type of T cell leukemia or lymphoma more specifically, accessibly, and safely than currently available therapies.
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