Abecma
idecabtagene vicleucel · BCMA CAR-TNot conducted (traditional); insertion site analysis of 20 clinical lots
Aucatzyl: genotox, carcinogenicity and repro: done or skipped?
obecabtagene autoleucel · CD19 CAR-T
Genotoxicity
Not conducted (third-generation SIN lentiviral vector, release criterion, long-term clinical monitoring for insertional mutagenesis)
“No nonclinical genotoxicity studies were conducted with obe-cel based on the genotoxic risks associated with the third-generation self-inactivating lentiviral vector used to produce obe-cel, acceptable release criterion, and inclusion of long-term clinical monitoring for insertional mutagenesis and clonality.”
Carcinogenicity
Not conducted (ICH S9; no murine CD19 cross-reactivity; murine T cells resist LV transformation)
“Carcinogenicity studies are not needed for indications falling under ICH S9 scope (advanced cancer). In addition, there is no cross-reactivity of the CD19-CAR T cells from Aucatzyl with the murine antigen.”
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
Literature-based insertional mutagenesis risk evaluation instead of insertion site analysis
“The literature-based risk evaluation of insertional mutagenesis instead of actual insertion site analysis is sufficient from a non-clinical perspective.”
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 (ICH S9; no pharmacologically relevant species)
“DART studies are not needed for indications falling under ICH S9 scope (advanced cancer) and no pharmacologically relevant animal species is available.”
Safety pharmacology
Not conducted; human-specific product with immune-related risks, immunocompromised models of limited relevance
“No safety pharmacology studies with obe-cel were conducted.”
Genotox: Ames
Not conducted (standard genotoxicity not applicable to ATMPs)
“Standard in vitro and in vivo genotoxicity studies are not applicable to ATMPs.”
Genotox: in vitro mammalian
Not conducted; relies on third-generation SIN lentiviral vector, release criterion and long-term clinical monitoring for insertional mutagenesis
“No nonclinical genotoxicity studies were conducted with obe-cel based on the genotoxic risks associated with the third-generation self-inactivating lentiviral vector used to produce obe-cel, acceptable release criterion, and inclusion of long-term clinical monitoring”
Genotox: in vivo
Not conducted (standard genotoxicity not applicable to ATMPs)
“Standard in vitro and in vivo genotoxicity studies are not applicable to ATMPs.”
Carcinogenicity model
Not conducted; oncogenesis testing in mice judged difficult as murine T cells resist LV-mediated transformation
“Moreover, evaluation of oncogenesis in e.g. mice would be difficult, considering the high resistance of murine T cells against transformation by LV-related genetic insertions.”
Carcinogenicity timing
Not required (ICH S9, advanced cancer)
“Carcinogenicity studies are not needed for indications falling under ICH S9 scope (advanced cancer).”
hERG / QT
Not conducted (no safety pharmacology studies)
“No safety pharmacology studies with obe-cel were conducted.”
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)
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