Abecma
idecabtagene vicleucel · BCMA CAR-TBCMA-specific IFN-γ release in vitro; CRS not modeled; expected depletion of normal plasma cells
Alofisel: which risks did reviewers probe?
darvadstrocel · Allogeneic adipose MSC
Immune & cytokine safety
Low T-cell recognition and delayed NK elimination in vitro; immunocompetent rats showed rejection-type inflammation
“Data generated in other toxicity studies show low potential for T-cell mediated eASC recognition, in vitro and delayed NK cell mediated elimination.”
Biodistribution & persistence
Rats: eASC persisted short term (day 14), restricted to rectum/jejunum locally; lungs after IV
“In conclusion, when administered locally human eASC is only persistent for a short period of time in rats.”
Modality-specific risk
Ectopic tissue formation and tumourigenicity (RMP potential risk); pulmonary embolism if systemic
“Ectopic tissue formation and tumourigenicity has therefore been included in the RMP as important potential risk and will be followed up with the agreed post-authorisation safety study (PASS).”
Anti-drug antibodies: animals
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Anti-drug antibodies: patients
Donor-specific antibodies generated; no apparent effect on efficacy or safety after single treatment (incidence not given)
“A specific risk associated with Alofisel use is the generation of Donor Specific Antibodies (DSA). Based on the current data, the generation of DSA does not appear to affect efficacy or safety after single treatment.”
Same question, other cell therapies
Amtagvi
lifileucel · TIL therapyNo immunotox/cytokine studies; literature shows anti-CD3-activated TIL cytotoxicity specific to autologous tumor, not heterologous targets
Aucatzyl
obecabtagene autoleucel · CD19 CAR-TNo nonclinical CRS/ICANS model; CRS and neurotoxicity judged clinically manageable; CAT19 showed higher TNF-α in vitro/in vivo
Breyanzi
lisocabtagene maraleucel · CD19 CAR-TIn vitro CD19-specific IFN-γ, IL-2, TNF-α release; EGFRt allows cetuximab-mediated CAR-T depletion
Carvykti
ciltacabtagene autoleucel · BCMA CAR-TCRS, TLS, MAS not investigated nonclinically; off-target CLDN9 binding seen only on overexpressing cells
ChondroCelect
characterised viable autologous cartilage cells · Autologous chondrocytesHuman/allogeneic chondrocytes caused immune response and poor repair in orthotopic model
Ebvallo
tabelecleucel · EBV-specific allogeneic T cellsNo cytokine or immunogenicity studies; low alloreactivity verified in release testing; CD20 not expressed (rituximab interaction unlikely)
Encelto
revakinagene taroretcel · CNTF (encapsulated RPE cell implant)Minipig/pig studies to 6 months showed no immune response to rhCNTF or cells; mild to moderate ocular inflammation
Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblastsNo alloimmune response in vitro; indirect allorecognition not evaluated; xenogeneic reaction to subcutaneous injection in rabbits
Holoclar
autologous corneal epithelial cells containing limbal stem cells · Autologous limbal stem cellsNo immunogenicity studies; no significant adaptive immune response in clinical setting
Kymriah
tisagenlecleucel · CD19 CAR-TNo cytokine/CRS studies; scFv bound only CD19 on 3550-protein array; no CD19 in human/cyno brain
Lantidra
donislecel · Allogeneic pancreatic isletsAllograft rejection without immunosuppression in mice; clinical HLA sensitization (donor-specific antibodies) risk
MACI
autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytesInflammation likely due to defect creation and possible immune response to porcine membrane
Omisirge
omidubicel · Expanded cord blood HPCNot assessed nonclinically (immunodeficient model); clinically GvHD dose-safety relationship flat
Provenge
sipuleucel-T · PAP-GM-CSF (autologous APC)Autoimmune prostatitis induced in rats (mild to moderate); non-prostate PAP-expressing tissues not fully examined; no robust data on autoimmunity risk
Rethymic
allogeneic processed thymus tissue · Allogeneic thymus tissueDonor-derived T cells declined as endogenous recipient T cells developed in rats; no dedicated immunotoxicity study
Ryoncil
remestemcel-L · Allogeneic BM-MSCLow-level alloantibody formation in baboons; in vitro ceMSC suppress T cells and shift cytokines (IFNg, IL-10 up, TNFa down)
Spherox
spheroids of autologous matrix-associated chondrocytes · Autologous chondrocyte spheroidsNo immunogenicity studies; enlarged popliteal lymph nodes in 2 sheep with allogeneic cells, possible immune response
StrataGraft
allogeneic cultured keratinocytes and dermal fibroblasts in murine collagen · Allogeneic keratinocytes + fibroblastsXenogeneic response possible in immunocompetent animals, so athymic mice used; no immunogenicity studies reported
Tecartus
brexucabtagene autoleucel · CD19 CAR-TCRS, neurotoxicity, MAS not investigated nonclinically; considered general CAR-T effects
Tecelra
afamitresgene autoleucel · MAGE-A4 TCR-TIn vitro cytokine-release assay for cytokine-storm risk, no concerns; no immunogenicity studies (wild-type human TCR)
Tregzi
allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + TconTregs suppress Tcon activation via contact and IL-2 inhibition; GVHD and weight loss in mice from Tcons; no cytokine release or immunotoxicity studies
Yescarta
axicabtagene ciloleucel · CD19 CAR-TCRS, TLS, MAS deemed not investigable nonclinically; CD19-dependent cytokine release in vitro
Zalmoxis
allogeneic T cells modified with HSV-TK / dLNGFR (nalotimagene carmaleucel) · HSV-TK suicide-gene T cellsGvHD is the key immune risk; no antigenicity/immunotoxicity studies; GCV suicide gene as mitigation
Zemcelpro
dorocubicel · UM171-expanded cord blood CD34+No immunogenicity/cytokine studies; DP2 not tested in vivo as GvHD expected in NSG mice from mature immune cells
Laviv
azficel-T · Autologous fibroblastsNot stated in public reviews