Abecma
idecabtagene vicleucel · BCMA CAR-TNo relevant species; NSG mouse xenografts and in vitro only
Tecelra: which tox species, and why?
afamitresgene autoleucel · MAGE-A4 TCR-T
Species
No relevant species; in vitro cross-reactivity/alloreactivity and murine xenograft pharmacology only
“Standard in vivo single-dose or repeat-dose toxicity studies were not conducted with afamitresgene autoleucel due to the lack of appropriate animal models for testing of human TCR engineered T-cells.”
Why that species
HLA-restricted human TCR: MHC mismatch with animals; humanized mice develop lethal xeno-GvHD within 8 weeks
“Because afamitresgene autoleucel is an autologous engineered-TCR T-cell therapy, there is a mismatch of MHC antigens between animal and human TCRs, so specificity cannot be assessed.”
Surrogate molecule
No surrogate; engineering an animal TCR judged uninformative for human TCR specificity/safety
“Engineering an animal TCR for use in animal model testing would also not reflect the specificity/safety profile of the human TCR, and therefore would be uninformative.”
Species: general tox
None; no in vivo toxicity studies (no appropriate animal model for human TCR-engineered T cells)
“Standard in vivo single-dose or repeat-dose toxicity studies were not conducted with afamitresgene autoleucel due to the lack of appropriate animal models for testing of human TCR engineered T-cells.”
Species: DART
Not conducted; acceptable based on product characteristics and safety profile
“No animal reproductive and developmental toxicity studies were conducted with TECELRA which is acceptable based on the product characteristics and safety profile.”
Species: carcinogenicity
Not conducted (no relevant animal models)
“Afamitresgene autoleucel is a human TCR engineered T-cell product, therefore conventional carcinogenicity studies were not performed due to the lack of relevant animal models.”
Surrogate used in
No surrogate used; an animal TCR was judged uninformative
“Engineering an animal TCR for use in animal model testing would also not reflect the specificity/safety profile of the human TCR, and therefore would be uninformative.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCImmunocompromised athymic nude rats (GLP); nude mice for tumourigenicity
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
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