Abecma
idecabtagene vicleucel · BCMA CAR-TNSG mice bearing subcutaneous BCMA+ human MM xenografts: dose-dependent anti-tumor activity and improved survival
Zemcelpro: animal efficacy model or human cells?
dorocubicel · UM171-expanded cord blood CD34+
Efficacy evidence
In vivo primary and secondary engraftment of UM171-cultured human cord blood CD34+ cells; in vitro expansion studies
“In vivo engraftment studies were conducted to show primary and secondary engraftment of UM171-cultured human CD34+ cord blood cells, thereby also evaluating the impact of changes in culture conditions.”
Why that model
UM171 has no activity on mouse HSCs, so a homologous murine product was not possible
“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).”
Reviewer's view of the efficacy data
No firm conclusions from nonclinical PD; efficacy must come from clinical studies
“Taken together, no firm conclusions can be drawn from the non-clinical primary PD data and therefore information on the efficacy of Zemcelpro should come from clinical studies.”
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
Yescarta
axicabtagene ciloleucel · CD19 CAR-TPublished surrogate anti-murine CD19 CAR T cells in lymphodepleted syngeneic CD19+ B-cell lymphoma mice
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