Case Report of a Fatal Serious Adverse Event Upon Administration of T Cells Transduced With a MART-1-specific T-cell Receptor

Mol Ther. 2015 Sep;23(9):1541-50. doi: 10.1038/mt.2015.60. Epub 2015 Apr 21.


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 irreversible neurologic damage. After T-cell infusion, levels of IL-6, IFN-γ, C-reactive protein (CRP), and procalcitonin increased to extreme levels, indicative of a cytokine release syndrome or T-cell-mediated inflammatory response. Infused T cells could be recovered from blood, broncho-alveolar lavage, ascites, and after autopsy from tumor sites and heart tissue. High levels of NT-proBNP indicate semi-acute heart failure. No cross reactivity of the modified T cells toward a beating cardiomyocyte culture was observed. Together, these observations suggest that high levels of inflammatory cytokines alone or in combination with semi-acute heart failure and epileptic seizure may have contributed substantially to the occurrence of the acute and lethal event. Protocol modifications to limit the risk of T-cell activation-induced toxicity are discussed.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Cell- and Tissue-Based Therapy / adverse effects*
  • Cell- and Tissue-Based Therapy / methods
  • Fatal Outcome
  • Female
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • MART-1 Antigen / immunology*
  • MART-1 Antigen / metabolism
  • Melanoma / diagnosis
  • Melanoma / genetics
  • Melanoma / immunology
  • Melanoma / therapy
  • Neoplasm Staging
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Cell Antigen Receptor Specificity / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transduction, Genetic


  • MART-1 Antigen
  • Receptors, Antigen, T-Cell