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Author
Pengfei Tang -
PI
Theodore Scott Nowicki
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Co-Author
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Title
Hypophosphatemia is Associated with Neurotoxicity Symptoms in CAR-T Cell Therapy
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Program
STTP
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Other Program (if not listed above)
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Abstract
Adoptive immune cell therapies, including genetically engineered chimeric antigen receptor (CAR)-T cell therapy have greatly transformed the landscape of cancer treatment for several cancers, including relapsed/refractory non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, and acute lymphoid leukemia [1]. While effective, CAR-T cell therapies can be limited by neurological cytokine release syndrome (N-CRS), which is characterized by confusion, dysphasia/aphasia, impaired fine motor skills, somnolence, and in more severe cases, seizures, motor weakness, cerebral edema, and coma [8]. N-CRS is currently managed through supportive care and high-dose corticosteroids. The use of corticosteroids is not ideal, given that the immunosuppression can potentially attenuate the anti-tumor activity of the treatment itself [8]. Previous studies dealing with refeeding syndrome, which can occur when administering nutrition to malnourished individuals, have demonstrated rapid evolution of hypophosphatemia due to an iatrogenic energetic crisis. The rapid introduction of carbohydrates causes an insulin surge that promotes rapid cellular uptake and use of glucose and phosphate, leading to extreme depletion of serum phosphorus, and onset of neuromuscular and psychiatric symptoms comparable to those seen in CAR-T patients experiencing N-CRS [2]. The goal of my project is to investigate the relationship between CAR-T cell neurotoxicity and serum phosphorus levels. I hypothesize that the increased metabolic demand of these highly activated genetically engineered immune cells is causing clinically significant hypophosphatemia, leading to neurotoxicity. If true, a safe, non-invasive serum phosphorus replenishment protocol can be introduced to prevent or reduce the severity of CAR T therapy-induced neurotoxicity.
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