Abecma
idecabtagene vicleucel · BCMA CAR-TNSG mice bearing subcutaneous BCMA+ human MM xenografts: dose-dependent anti-tumor activity and improved survival
Yescarta: animal efficacy model or human cells?
axicabtagene ciloleucel · CD19 CAR-T
Efficacy evidence
Published surrogate anti-murine CD19 CAR T cells in lymphodepleted syngeneic CD19+ B-cell lymphoma mice
“To evaluate CD19-specific anti-tumor activity in vivo, an analogous murine CAR construct recognizing the murine CD19 molecule was evaluated in a lymphodepleted syngeneic mouse model of CD19+ B cell lymphoma.”
Why that model
FMC63 scFv recognizes human but not murine CD19, so an anti-murine CD19 CAR was used
“The scFv construct used to manufacture KTE-C19 recognizes human, but not murine CD19. Therefore, the NCI investigators developed an anti-murine CD19 CAR construct to administer in a syngeneic mouse model of B cell lymphoma in proof-of-concept experiments that also evaluated general safety.”
Reviewer's view of the efficacy data
EMA: package limited by animal models but adequate
“The non-clinical development package provided for KTE-C19 was limited due to the type of product and the limitations of animal models available for investigating pharmacodynamics, pharmacokinetics, and toxicity aspects of KTE-C19, but it was considered adequate.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCTNBS-induced colitis mice: dose-dependent improved survival and body weight; no anal fistula model
Amtagvi
lifileucel · TIL therapyPublished literature only: tumor-derived lymphocytes with Cy and IL-2 in murine colon adenocarcinoma and sarcoma metastasis models
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TSystemic human tumor xenograft mouse model: single IV dose of obe-cel significantly reduced tumor burden by Day 12
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TRaji Burkitt's lymphoma-bearing NOD/SCID IL-2Rγnull xenograft mice
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TImmunodeficient (NCG) mice engrafted with human multiple myeloma cells: dose-dependent anti-tumor activity and survival
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesEctopic nu/nu mouse model and orthotopic goat cartilage-defect model (ChondroCelect-like goat cells)
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsSCID mice with EBV+ BLCL-induced B cell lymphomas (IP/SC) treated with autologous tabelecleucel
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)rcd1 dog model of retinitis pigmentosa: NT-501 implant protected outer nuclear layer from photoreceptor loss
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsFull-thickness wound in athymic (nude) mice grafted with Apligraf
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNo product-specific pharmacology studies; published rat LSCD studies with similar fibrin-cultured limbal cells as proof of principle
Kymriah
tisagenlecleucel · CD19 CAR-TMice bearing human primary pre-B ALL xenografts: CTL019 improved survival vs mock T cells
Lantidra
donislecel · Allogeneic pancreatic isletsLiterature only: animal allogeneic/syngeneic islets with immunosuppressants in diabetic mice, rats and NHPs; no studies with the product
Laviv
azficel-T · Autologous fibroblastsLiterature only: animal analog fibroblasts in immunocompetent animals and human fibroblasts in immunodeficient mice; product not tested
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesAnalogous MACI (animal cells on same membrane) in critical-sized knee/stifle cartilage defects in rabbits and horses: improved repair vs membrane alone or empty defect
Omisirge
omidubicel · Expanded cord blood HPCHuman bone marrow engraftment of NAM-cultured cord blood cells in irradiated NOD/SCID mice; in vitro migration and phenotype assays
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Rodent surrogates: rat APCs with rPAP-rGM-CSF inducing prostate-specific inflammation; antigen-loaded APCs protecting mice against tumour challenge
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueAllogeneic neonatal thymus transplanted into nude rats (engraftment, endogenous T cell development)
Ryoncil
remestemcel-L · Allogeneic BM-MSCHuman ceMSC co-cultured with allogeneic immune cells (T cell suppression, cytokine modulation); no animal GVHD model
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsImmunodeficient mice (human spheroids) plus minipig pilot and 6-month Merino sheep studies with analogously produced autologous spheroids
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsNo nonclinical pharmacology studies; efficacy claims rest on clinical data
Tecartus
brexucabtagene autoleucel · CD19 CAR-TSurrogate anti-murine CD19 CAR T cells in lymphodepleted syngeneic CD19+ B-cell lymphoma mice
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TMurine tumor xenograft studies showing dose-dependent tumor control
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconXenogeneic GVHD model in sub-lethally irradiated immunodeficient mice: human Tcons with human Tregs gave dose-dependent GVHD inhibition
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsXenogeneic GvHD models in NOD/SCID mice comparing MM-TK with unmanipulated PBL
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+In vivo primary and secondary engraftment of UM171-cultured human cord blood CD34+ cells; in vitro expansion studies