Abecma
idecabtagene vicleucel · BCMA CAR-TBCMA-specific IFN-γ release in vitro; CRS not modeled; expected depletion of normal plasma cells
Aucatzyl: which risks did reviewers probe?
obecabtagene autoleucel · CD19 CAR-T
Immune & cytokine safety
No nonclinical CRS/ICANS model; CRS and neurotoxicity judged clinically manageable; CAT19 showed higher TNF-α in vitro/in vivo
“Known risks of CAR T cell therapies (e.g., CRS or neurotoxicity) can be clinically monitored and managed.”
Biodistribution & persistence
No dedicated PK/biodistribution; CAR T cells in blood and bone marrow at Day 16 in NSG mice; persistence assessed clinically
“Traditional non-clinical pharmacokinetic studies (absorption, distribution, metabolism, excretion and in vitro drug-drug interaction) have not been conducted because obe-cel is an autologous gene therapy product and there is no pharmacologically relevant species.”
Modality-specific risk
LV insertional mutagenesis/secondary malignancy (literature-based assessment), bystander transduction, follicular DC on-target off-tumor depletion
“However, it is also explained that the risk of transformation and oncogenesis with the current third generation SIN LVs and moderately active non-viral promoters is low (but not zero), especially in terminally differentiated cell types such as T cells.”
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
Treatment-induced anti-CD19 CAR antibodies 1.6%; pre-infusion positive 8.7%
“In the FELIX study, 8.7% (11/127) of patients tested positive for anti-CD19 CAR antibodies pre-infusion. Treatment induced anti-CD19 CAR antibodies were detected in 1.6% (2/127) of patients.”
Same question, other cell therapies
Alofisel
darvadstrocel · Allogeneic adipose MSCLow T-cell recognition and delayed NK elimination in vitro; immunocompetent rats showed rejection-type inflammation
Amtagvi
lifileucel · TIL therapyNo immunotox/cytokine studies; literature shows anti-CD3-activated TIL cytotoxicity specific to autologous tumor, not heterologous targets
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