Car T Cells Toxicity

Car t cell toxicity.

Car t cells toxicity. Early data show car nk cells potential to overcome car t toxicity and takeda is interested data from 11 patients in an md anderson study of a cell therapy that uses natural killer nk cells. The cytokines implicated in crs may be directly produced by the infused car t cells or other immune cells such as macrophages that might produce cytokines in response to cytokines produced by the infused car t cells. A huge concern when using car t cells is the on target off tumor toxicity which results in the destruction of normal tissues that unfortunately also express the target antigen. Consequently complete car t cell therapy includes elements where the toxicity profile is well known but also includes the car t cell itself for which toxicity profiles are largely unknown.

T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor car. Most notably car t cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. With recent reports of adverse events associated with car t cell therapy there is now concern that current preclinical models may not be fit for purpose with respect to car t cell toxicity profiling. Current management and future directions hemasphere.

A barrier to widespread use of car t cell therapy is toxicity primarily cytokine release syndrome crs and neurologic toxicity. Clinical and laboratory work up similar to the infusion of stem cell grafts and other cellular products infusion of car t cell products is generally safe but some precautions are needed. The most common acute toxicity of car t cells is crs. 1 10 in addition car t cells are frequently found in cerebrospinal fluid of patients with neurotoxicity.

Like crs cytokines chemokines and degree of car t cell expansion have been associated with severity of neurotoxicity. Authors lucrecia yáñez 1 2 miriam sánchez escamilla 2 3 miguel angel perales 3 4 affiliations 1 department of hematology university hospital marqués de. However it is unclear why car t cells traffic to central nervous system cns in the absence of disease. Monitoring car t cell toxicity.