Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Alofisel: genotox, carcinogenicity and repro: done or skipped?
darvadstrocel · Allogeneic adipose MSC
Genotoxicity
Not conducted; cell-based product does not interact with DNA
“Genotoxicity studies are not applicable for the product, considering the cell-based nature of the product, which precludes interaction directly with DNA or other chromosomal material.”
Carcinogenicity
Not conducted (conventional); in vitro senescence/karyotype/soft agar and mouse tumourigenicity, no tumours
“In in vivo tumourigenicity tests, nude mice administered a subcutaneous injection of eASC at various population doubling levels, equal to levels of product for clinical use, all survived to scheduled sacrifice and no tumour-formation was observed.”
Instead of carcinogenicity
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Instead of genotoxicity
Not applicable: cells not genetically modified
“Genotoxicity studies are not applicable for the product, considering the cell-based nature of the product, which precludes interaction directly with DNA or other chromosomal material.”
DRG histopathology
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Reproductive & developmental
Not conducted; no migration into reproductive organs in biodistribution
“Reproductive and developmental toxicity studies have not been performed for Alofisel because preclinical biodistribution studies indicated no migration and integration of eASC into reproductive organs”
Safety pharmacology
CNS: functional observational battery in rats showed no effect; CV/respiratory not performed
“eASC treatment did not affect any of the neurological parameters evaluated in the Functional Observational Battery Test”
Genotox: Ames
Not conducted (cell-based product does not interact with DNA)
“Genotoxicity studies are not applicable for the product, considering the cell-based nature of the product, which precludes interaction directly with DNA or other chromosomal material.”
Genotox: in vitro mammalian
Not conducted; karyotype normal diploid in expanded cells
“Analysis revealed normal male or female diploid karyotypes.”
Genotox: in vivo
Not conducted (cell-based product does not interact with DNA)
“Genotoxicity studies are not applicable for the product, considering the cell-based nature of the product, which precludes interaction directly with DNA or other chromosomal material.”
Carcinogenicity model
Subcutaneous tumourigenicity in nude mice: no tumours; in vitro senescence, telomerase, c-myc, soft agar negative
“In in vivo tumourigenicity tests, nude mice administered a subcutaneous injection of eASC at various population doubling levels, equal to levels of product for clinical use, all survived to scheduled sacrifice and no tumour-formation was observed.”
Carcinogenicity timing
No standard bioassay; in vivo nude mouse tumourigenicity study (no tumours) completed before the marketing application
“In in vivo tumourigenicity tests, nude mice administered a subcutaneous injection of eASC at various population doubling levels, equal to levels of product for clinical use, all survived to scheduled sacrifice and no tumour-formation was observed.”
hERG / QT
Not conducted (no cardiovascular/respiratory safety pharmacology)
“Cardiovascular or respiratory safety pharmacology studies were not performed for eASC which was considered acceptable by the CAT.”
Same question, other cell therapies
Amtagvi
lifileucel · TIL therapyNot conducted (not warranted given product characteristics and biological activity)
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNot conducted (third-generation SIN lentiviral vector, release criterion, long-term clinical monitoring for insertional mutagenesis)
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNot conducted (traditional); lentiviral integration site mapping instead
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TNot conducted (classical); lentiviral integration site analysis instead
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNot conducted (per cell-based product guideline)
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsNot conducted (ICH S6(R1)); non-genetically engineered cells
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Done: ISO-10993 battery (bacterial, mammalian cell, mouse micronucleus on device extracts), negative
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNot conducted (nature of product and clinical experience)
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNot conducted (classical); in vitro karyotype analysis of cells
Kymriah
tisagenlecleucel · CD19 CAR-TNot conducted (classical); lentiviral integration site analysis on 14 donor products
Lantidra
donislecel · Allogeneic pancreatic isletsNot conducted
Laviv
azficel-T · Autologous fibroblastsNot conducted (autologous nature, prior human experience)
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesNot conducted on cells; four studies on collagen membrane were non-mutagenic
Omisirge
omidubicel · Expanded cord blood HPCNo standard genotox; cytogenetic/karyotype analyses of CF and NF showed no clonal aneuploidy
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Not conducted (autologous nature of product)
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNot conducted
Ryoncil
remestemcel-L · Allogeneic BM-MSCNot conducted (not warranted)
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNot conducted (per cell-based product guideline)
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNot conducted
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNot conducted (traditional); vector integration site analysis performed instead
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TNot conducted (no test models or relevant species); integration site analysis showed polyclonal products, no selective insertion
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNot conducted
Yescarta
axicabtagene ciloleucel · CD19 CAR-TNot conducted; literature review of retroviral-transduced T-cell transformation risk instead
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsNot conducted; in vitro retroviral integration site analysis instead
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Done for residual UM171 only (Ames, CHO micronucleus negative) plus cytogenetics of treated cells; none for cells