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Atlas/Cell therapy/Tregzi/Risks

Tregzi: which risks did reviewers probe?

allogeneic Treg immunotherapy with HSPC and T cells (Orca-T) · Allogeneic Treg + HSPC + Tcon
Check my plan vs. these
Immune & cytokine safety
Tregs suppress Tcon activation via contact and IL-2 inhibition; GVHD and weight loss in mice from Tcons; no cytokine release or immunotoxicity studies
“No safety/toxicology studies were conducted to assess additional safety endpoints, such as immunotoxicity and local tolerance, for TREGZI.”
✓ VerifiedFDA pharmacology/toxicology review, p. 37Source ↗
Biodistribution & persistence
No cell distribution studies conducted
“No nonclinical studies were conducted to evaluate cell distribution of TREGZI.”
✓ VerifiedFDA pharmacology/toxicology review, p. 36Source ↗
Modality-specific risk
GVHD from donor Tcons and preservation of graft-versus-leukemia; Treg:Tcon ratio and timing; leachables from bags
“Data from this study provided the scientific rationale for administering Tregs two days earlier than Tcons clinically.”
✓ VerifiedFDA pharmacology/toxicology review, p. 3Source ↗

Same question, other cell therapies

Abecma

idecabtagene vicleucel · BCMA CAR-T
BCMA-specific IFN-γ release in vitro; CRS not modeled; expected depletion of normal plasma cells

Alofisel

darvadstrocel · Allogeneic adipose MSC
Low T-cell recognition and delayed NK elimination in vitro; immunocompetent rats showed rejection-type inflammation

Amtagvi

lifileucel · TIL therapy
No immunotox/cytokine studies; literature shows anti-CD3-activated TIL cytotoxicity specific to autologous tumor, not heterologous targets

Aucatzyl

obecabtagene autoleucel · CD19 CAR-T
No nonclinical CRS/ICANS model; CRS and neurotoxicity judged clinically manageable; CAT19 showed higher TNF-α in vitro/in vivo

Breyanzi

lisocabtagene maraleucel · CD19 CAR-T
In vitro CD19-specific IFN-γ, IL-2, TNF-α release; EGFRt allows cetuximab-mediated CAR-T depletion

Carvykti

ciltacabtagene autoleucel · BCMA CAR-T
CRS, TLS, MAS not investigated nonclinically; off-target CLDN9 binding seen only on overexpressing cells

ChondroCelect

characterised viable autologous cartilage cells · Autologous chondrocytes
Human/allogeneic chondrocytes caused immune response and poor repair in orthotopic model

Ebvallo

tabelecleucel · EBV-specific allogeneic T cells
No 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 + fibroblasts
No 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 cells
No immunogenicity studies; no significant adaptive immune response in clinical setting

Kymriah

tisagenlecleucel · CD19 CAR-T
No cytokine/CRS studies; scFv bound only CD19 on 3550-protein array; no CD19 in human/cyno brain

Lantidra

donislecel · Allogeneic pancreatic islets
Allograft rejection without immunosuppression in mice; clinical HLA sensitization (donor-specific antibodies) risk

MACI

autologous cultured chondrocytes on porcine collagen membrane · Autologous chondrocytes
Inflammation likely due to defect creation and possible immune response to porcine membrane

Omisirge

omidubicel · Expanded cord blood HPC
Not 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 tissue
Donor-derived T cells declined as endogenous recipient T cells developed in rats; no dedicated immunotoxicity study

Ryoncil

remestemcel-L · Allogeneic BM-MSC
Low-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 spheroids
No 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 + fibroblasts
Xenogeneic response possible in immunocompetent animals, so athymic mice used; no immunogenicity studies reported

Tecartus

brexucabtagene autoleucel · CD19 CAR-T
CRS, neurotoxicity, MAS not investigated nonclinically; considered general CAR-T effects

Tecelra

afamitresgene autoleucel · MAGE-A4 TCR-T
In vitro cytokine-release assay for cytokine-storm risk, no concerns; no immunogenicity studies (wild-type human TCR)

Yescarta

axicabtagene ciloleucel · CD19 CAR-T
CRS, 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 cells
GvHD 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 fibroblasts
Not stated in public reviews

Summary across all 27 cell therapies →