Abecma
idecabtagene vicleucel · BCMA CAR-TNSG mice bearing subcutaneous BCMA+ human MM xenografts: dose-dependent anti-tumor activity and improved survival
Kymriah: animal efficacy model or human cells?
tisagenlecleucel · CD19 CAR-T
Efficacy evidence
Mice bearing human primary pre-B ALL xenografts: CTL019 improved survival vs mock T cells
“A series of studies in mice bearing human primary pre-B ALL conducted to evaluate anti-tumor activity of CTL019 derived from different healthy human donors showed significantly improved survival in the tumor-bearing mice receiving intravenous (i.v.) injection of CTL019 at 2x106 cells/mouse as compared to the mock T cell administered animals.”
Why that model
Patient-specific human T-cell product cannot be given to immunocompetent animals; xenograft in immunodeficient mice used
“The lack of single-dose toxicity studies is acceptable, since tisagenlecleucel is a patient specific product, which is not appropriate to administer to immune competent animals.”
Reviewer's view of the efficacy data
Accepted; ALL-only xenograft pharmacology (no DLBCL studies) acceptable given clinical experience
“The lack of non-clinical pharmacology studies with DLBCL cells is acceptable based on the clinical experience with this indication.”
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
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
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