Abstract:Here, we describe a fatal serious adverse event observed in a patient infused with autologous T-cell receptor (TCR) transduced T cells. This TCR, originally obtained from a melanoma patient, recognizes the well-described HLA-A*0201 restricted 26-35 epitope of MART-1, and was not affinity enhanced. Patient 1 with metastatic melanoma experienced a cerebral hemorrhage, epileptic seizures, and a witnessed cardiac arrest 6 days after cell infusion. Three days later, the patient died from multiple organ failure and … Show more
“…The adoptive transfer of TCR transgenic T cells and CAR T cells can cause severe immunotoxicity owing to cytokine release upon target recognition 95,96 . Cytokine-release syndrome can be effectively managed with cytokine blockade 29 .…”
“…The adoptive transfer of TCR transgenic T cells and CAR T cells can cause severe immunotoxicity owing to cytokine release upon target recognition 95,96 . Cytokine-release syndrome can be effectively managed with cytokine blockade 29 .…”
“…One patient died from cytokine release with a clinical syndrome like that observed with CAR T cells (van den Berg et al, 2015). Whether MART-1 is a valid target for engineered T cells remains an open question.…”
Chimeric antigen receptor (CAR) T cells have proven that engineered immune cells can serve as a powerful new class of cancer therapeutics. Clinical experience has helped to define the major challenges that must be met to make engineered T cells a reliable, safe, and effective platform that can be deployed against a broad range of tumors. The emergence of synthetic biology approaches for cellular engineering is providing us with a broadly expanded set of tools for programming immune cells. We discuss how these tools could be used to design the next generation of smart T cell precision therapeutics.
“…The CD19 CAR-T therapy always induces transient or prolonged lack of B cells, resulting in adaptive immunoglobulin deficiency [83]. Severe toxicity was reported for multiple tissues damage including the skin, eyes, and ears in a late stage clinical trial enrolled 36 patients with metastatic melanoma received MART-1 or gp100-specific TCR-T cells [84,85].…”
Section: The On-target/off-tumor Toxicity Relates To Antigens Both Onmentioning
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