Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Zemcelpro: genotox, carcinogenicity and repro: done or skipped?
dorocubicel · UM171-expanded cord blood CD34+
Genotoxicity
Done for residual UM171 only (Ames, CHO micronucleus negative) plus cytogenetics of treated cells; none for cells
“An AMES and a micronucleus test were conducted to assess the genetic safety of UM171”
Carcinogenicity
Not conducted
“Carcinogenicity studies were not submitted, which can be agreed.”
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
“An AMES and a micronucleus test were conducted to assess the genetic safety of UM171”
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 reproductive and developmental toxicity studies were presented.”
Safety pharmacology
In vitro hERG assay with residual UM171 (non-GLP), no relevant block
“UM171 appeared not to have a relevant blocking effect on the channel activity.”
Genotox: Ames
Negative (UM171; non-GLP and GLP Ames)
“Genotoxicity of UM171 was evaluated in a non-GLP AMES test at first with no mutagenic response observed. After receiving scientific advice from EMA the applicant conducted an additional GLP compliant AMES test in accordance with ICH S2 and OECD guidance with no mutagenic response observed.”
Genotox: in vitro mammalian
In vitro micronucleus in CHO cells (UM171): negative
“UM171 was considered to be negative, i.e. the test item did not induce chromosome breaks and/or loss in cultured CHO cells.”
Genotox: in vivo
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.
Carcinogenicity model
Not conducted; no neoplasia seen in NSG mouse studies of UM171-expanded cells
“There was also no indication of neoplasia in the in vivo toxicological studies of UM171 expanded cells in NSG mice.”
Carcinogenicity timing
Not required (ICH S9, advanced cancer)
“The applicant did not perform any carcinogenicity studies, which is in line with ICH S9 since the product is to be used in patients with advanced cancer.”
hERG / QT
UM171 (0.1-10 µM): non-significant current decrease; no relevant hERG block (non-GLP)
“UM171 (0.1 to 10 µM) did decrease the current through the channel, but this was not statistically significant compared to baseline. Taken together, UM171 appeared not to have a relevant blocking effect on the channel activity.”
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
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