Ebvallo

“Safety pharmacology studies were not conducted due to the species-specific nature of tabelecleucel and the limited applicability of non-human toxicology models.”

“Because SCID mice are unable to generate functional lymphocytes, engraftment and growth of human lymphocytes and several human tumours are possible.”

“Inoculation of SCID mice with EBV+ BLCL results in development of EBV-induced immunoblastic B cell lymphomas with characteristics similar to EBV-PTLD arising in immunocompromised hosts”

“Two of 5 mice in each group had complete tumour regression and survived > 5 months after tabelecleucel treatment.”

“Studies conducted in immunodeficient animal models for EBV+ PTLD revealed no overt signs of toxicity (e.g. loss of activity or weight loss) associated with a single dose of tabelecleucel.”

“The IV inoculation of 107 EBV-specific CTL resulted in improved survival of SCID mice (n = 5)”

“In accordance with ICH S6(R1), genotoxicity studies with tabelecleucel were not conducted.”

“standard carcinogenicity bioassays are generally inappropriate for”

“Due to the highly species-specific nature of the pharmacology associated with tabelecleucel, nonclinical reproductive/developmental toxicity studies were not submitted with this application.”

“Safety pharmacology studies were not conducted due to the species-specific nature of tabelecleucel and the limited applicability of non-human toxicology models.”

“Studies conducted in immunodeficient animal models for EBV+ PTLD revealed no overt signs of toxicity (e.g. loss of activity or weight loss) associated with a single dose of tabelecleucel.”

“Ebvallo is tested for specificity of lysis of EBV+ targets, T-cell HLA restriction of specific lysis, and verification of low alloreactivity.”

“Migration and infiltration occurred into fully HLA-matched tumours and was absent from mismatched tumours.”

“Taken together, this data showed the lack of transmission and uncontrolled proliferation of infectious EBV to MCBC and autologous T cell depleted PBMC.”