Abecma
idecabtagene vicleucel · BCMA CAR-TNo relevant species; NSG mouse xenografts and in vitro only
Zemcelpro: which tox species, and why?
dorocubicel · UM171-expanded cord blood CD34+
Species
Female sub-lethally irradiated NSG mice (human cells); UM171 compound PK/tox in NSG mouse, rat, cynomolgus monkey
“All in vivo studies have been conducted with female NSG mice.”
Why that species
UM171 has no activity on mouse HSCs; human cells in immunocompromised NSG mice needed (homologous murine product not possible)
“because the applicant explained that UM171 had no activity on mouse HSCs (i.e. homologous murine product not possible).”
Surrogate molecule
No surrogate; human product tested in NSG mice
“The human cell product has been used in these immunocompromised animals”
Species: general tox
UM171 only: rat (single dose) and cynomolgus monkey (3 doses, 7-day washout)
“Intravenous administration at doses 8,000-20,000 times higher than the estimated human exposure to UM171 demonstrated no toxicity in rats (single-dose study) or cynomolgus monkeys (administrated 3 times with a 7-day washout period before testing the next dose).”
Species: DART
Not conducted (not for use in pregnancy; minimal residual UM171)
“No reproductive and developmental toxicity studies on either UM171 or dorocubicel were conducted by the applicant. The applicant contended that such studies are unnecessary as ECT-001-CB is not recommended for use in pregnant women, and only minimal residual amounts of UM 171 were detected in dorocubicel.”
Species: carcinogenicity
Not conducted (ICH S9; advanced cancer population)
“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.”
Surrogate used in
No surrogate; UM171 inactive on mouse HSCs, so human cells used in immunocompromised mice
“The human cell product has been used in these immunocompromised animals, because the applicant explained that UM171 had no activity on mouse HSCs (i.e. homologous murine product not possible).”
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
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