Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Kymriah: genotox, carcinogenicity and repro: done or skipped?
tisagenlecleucel · CD19 CAR-T
Genotoxicity
Not conducted (classical); lentiviral integration site analysis on 14 donor products
“Genotoxicity Studies: Classical genotoxicity studies were not conducted. The provided LV integration site analysis may be relevant for evaluation of potential genotoxicity.”
Carcinogenicity
Not conducted (rodent models not appropriate for insertional mutagenesis of modified cells)
“Genotoxicity assays and carcinogenicity studies in rodents are not appropriate to assess the risk of insertional mutagenesis for genetically modified cell therapy products.”
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
Lentiviral insertion site analysis on CTL019 from 14 donors (2 healthy, 12 patients)
“A genomic insertion site analysis was performed on CTL019 from 14 individual donors (2 healthy donors and 12 patients representing pediatric ALL-derived and diffuse large B-cell lymphoma (DLBCL)-derived cells).”
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 preclinical reproductive studies were conducted with CTL019 to assess whether it can cause fetal harm when administered to a pregnant woman.”
Safety pharmacology
Not conducted
“No safety pharmacology studies have been conducted (see non-clinical discussion).”
Genotox: Ames
Not conducted (no classical genotoxicity studies)
“Genotoxicity Studies: Classical genotoxicity studies were not conducted. The provided LV integration site analysis may be relevant for evaluation of potential genotoxicity.”
Genotox: in vitro mammalian
Not conducted; lentiviral integration site analysis provided instead
“Genotoxicity Studies: Classical genotoxicity studies were not conducted. The provided LV integration site analysis may be relevant for evaluation of potential genotoxicity.”
Genotox: in vivo
Not conducted (no classical genotoxicity studies)
“Genotoxicity Studies: Classical genotoxicity studies were not conducted. The provided LV integration site analysis may be relevant for evaluation of potential genotoxicity.”
Carcinogenicity model
Not conducted; immunocompromised mice showed no abnormal growth or clonal expansion up to 7 months; integration site analysis
“In vivo studies in immunocompromised mice did not show signs of abnormal cell growth or signs of clonal cell expansion for up to 7 months, which represents the longest meaningful observation period for immunocompromised mouse models.”
Carcinogenicity timing
Not required: rodent carcinogenicity studies not appropriate for genetically modified cell therapy
“Genotoxicity assays and carcinogenicity studies in rodents are not appropriate to assess the risk of insertional mutagenesis for genetically modified cell therapy products.”
hERG / QT
Not conducted (no safety pharmacology studies)
“No safety pharmacology studies have been conducted (see non-clinical discussion).”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCNot conducted; cell-based product does not interact with DNA
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
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