Abecma
idecabtagene vicleucel · BCMA CAR-TNo relevant species; NSG mouse xenografts and in vitro only
Alofisel: which tox species, and why?
darvadstrocel · Allogeneic adipose MSC
Species
Immunocompromised athymic nude rats (GLP); nude mice for tumourigenicity
“The applicant has chosen immunocompromised athymic rats to perform the biodistribution, toxicology and tumourigenicity studies.”
Why that species
Athymic rats minimise rejection of human cells and extend persistence; immunocompetent rats rejected the cells
“in order to minimize the immune recognition and potential rejection of human eASC in the experimental animal models and to extend Cx601 persistence”
Surrogate molecule
No surrogate; human eASC tested in immunodeficient rats and mice (xenogeneic)
“Human eASC preparations from six donors (3 men and 3 women) were expanded to population doubling levels equal to levels of product for clinical use.”
Species: general tox
Athymic nude rat (perianal; 3- and 6-month post-dose observation) plus IV study
“Two repeat-dose toxicity studies were conducted with human eASC in male and female athymic nude rats (Crl:NIH-Foxn1rnu) via the perianal route, a study with a 3-month post-dose observation period and a study with a 6-month post-dose observation period.”
Species: DART
Not conducted; biodistribution showed no migration to reproductive organs
“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 following administration of eASC via different routes.”
Species: carcinogenicity
Nude mouse subcutaneous tumourigenicity test (no conventional carcinogenicity study)
“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.”
Surrogate used in
No surrogate used; human eASC tested in immunocompromised athymic rats
“The applicant has chosen immunocompromised athymic rats to perform the biodistribution, toxicology and tumourigenicity studies.”
Same question, other cell therapies
Amtagvi
lifileucel · TIL therapyNo animal studies with product; published murine and human TIL literature only
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNo relevant species; no in vivo tox. NSG xenograft (pharmacology) and human tissue cross-reactivity only
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TNo relevant species; in vitro and NSG mouse xenograft only
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TNo relevant species; NCG mouse xenografts, non-GLP NHP pilot with autologous NHP CAR-T
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesNude mouse (ectopic), sheep and goat (orthotopic); non-GLP combined PD/PK/tox
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsSCID mice (EBV+ lymphoma xenograft, literature/PD); no tox species
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Minipig, pig and rabbit (ocular tox/PK); rcd1 dog for pharmacology; rat and rabbit for rhCNTF DART
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsAthymic (nude) mice for pharmacology; rabbits, guinea pigs, mice for biocompatibility
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNo animal species; abridged programme of in vitro tumorigenicity assays and literature
Kymriah
tisagenlecleucel · CD19 CAR-TNo relevant species; immunodeficient mouse B-ALL xenograft (non-GLP) only
Lantidra
donislecel · Allogeneic pancreatic isletsNo studies with product; literature only (diabetic mice, rats, NHP, pigs)
Laviv
azficel-T · Autologous fibroblastsNo preclinical or toxicology studies conducted with the product
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesRabbit and horse, with analogous MACI (species-matched autologous cells on ACI-Maix)
Omisirge
omidubicel · Expanded cord blood HPCImmunodeficient irradiated NOD/SCID mouse only (xenogeneic human cells)
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)No conventional tox species; rat and mouse proof-of-concept studies with rodent surrogate products
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueNo relevant species; nude rat pharmacology studies only, no tox
Ryoncil
remestemcel-L · Allogeneic BM-MSCRat, baboon and pig using species-specific surrogate ceMSC
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsImmunodeficient (SCID/NSG) mice, Goettingen minipig, Merino sheep; no conventional tox
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsAthymic nude mice only (immunodeficient wound model)
Tecartus
brexucabtagene autoleucel · CD19 CAR-TNo relevant species; in vitro and syngeneic mouse surrogate CAR-T only
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TNo relevant species; in vitro cross-reactivity/alloreactivity and murine xenograft pharmacology only
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconNo tox species; sublethally irradiated immunodeficient mice (xenogeneic GVHD proof-of-concept) plus published murine literature
Yescarta
axicabtagene ciloleucel · CD19 CAR-TNo relevant species; syngeneic mouse lymphoma model with murine surrogate CAR-T (published, non-GLP)
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsImmunodeficient NOD/SCID mice (GvHD xenograft models); no conventional tox species
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+Female sub-lethally irradiated NSG mice (human cells); UM171 compound PK/tox in NSG mouse, rat, cynomolgus monkey