CRISPR-edited, healthy-donor T cells engineered with an anti-CD19 STAR receptor inserted at the TRAC locus and knockouts of TRAC, HLA-A/B, CIITA, and PD-1 to target CD19+ B cells while reducing rejection and GvHD.
Allogeneic CRISPR-edited donor T cells engineered with an anti‑CD19 STAR receptor inserted at the TRAC locus redirect TCR–CD3 signaling to recognize and kill CD19+ B cells independent of MHC. Knockout of TRAC removes the endogenous TCR to reduce GvHD; HLA‑A/B and CIITA knockouts lower allorecognition and host rejection by minimizing MHC I/II expression; and PD‑1 knockout enhances resistance to checkpoint-mediated inhibition, improving antitumor activity against CD19+ malignancies.
NO
INDIRECT
The engineered T cells kill CD19+ B cells via STAR-receptor redirected TCR/CD3 signaling and perforin/granzyme cytotoxicity. PD-1 is knocked out on the therapeutic T cells and is not a killing target; PD-1-expressing cells are not directly attacked.
CRISPR-edited, healthy-donor T cells engineered with an anti-CD19 STAR receptor inserted at the TRAC locus and knockouts of TRAC, HLA-A/B, CIITA, and PD-1 to target CD19+ B cells while reducing rejection and GvHD.
Allogeneic CRISPR-edited donor T cells engineered with an anti‑CD19 STAR receptor inserted at the TRAC locus redirect TCR–CD3 signaling to recognize and kill CD19+ B cells independent of MHC. Knockout of TRAC removes the endogenous TCR to reduce GvHD; HLA‑A/B and CIITA knockouts lower allorecognition and host rejection by minimizing MHC I/II expression; and PD‑1 knockout enhances resistance to checkpoint-mediated inhibition, improving antitumor activity against CD19+ malignancies.
NO
INDIRECT
The product T cells kill CD19+ B cells via a STAR receptor that redirects TCR–CD3 signaling (perforin/granzyme cytolysis). TRAC is knocked out as an editing site and is not a killing target; cells expressing TRAC are not targeted.
CRISPR-edited, healthy-donor T cells engineered with an anti-CD19 STAR receptor inserted at the TRAC locus and knockouts of TRAC, HLA-A/B, CIITA, and PD-1 to target CD19+ B cells while reducing rejection and GvHD.
Allogeneic CRISPR-edited donor T cells engineered with an anti‑CD19 STAR receptor inserted at the TRAC locus redirect TCR–CD3 signaling to recognize and kill CD19+ B cells independent of MHC. Knockout of TRAC removes the endogenous TCR to reduce GvHD; HLA‑A/B and CIITA knockouts lower allorecognition and host rejection by minimizing MHC I/II expression; and PD‑1 knockout enhances resistance to checkpoint-mediated inhibition, improving antitumor activity against CD19+ malignancies.
NO
INDIRECT
The engineered T cells kill CD19+ cells via STAR receptor–redirected TCR–CD3 signaling. HLA-A is not a recognized target for killing (it is knocked out on the infused T cells to reduce alloreactivity), so HLA-A–expressing cells are not directly killed unless they also express CD19, in which case killing is driven by CD19, not HLA-A.
CRISPR-edited, healthy-donor T cells engineered with an anti-CD19 STAR receptor inserted at the TRAC locus and knockouts of TRAC, HLA-A/B, CIITA, and PD-1 to target CD19+ B cells while reducing rejection and GvHD.
Allogeneic CRISPR-edited donor T cells engineered with an anti‑CD19 STAR receptor inserted at the TRAC locus redirect TCR–CD3 signaling to recognize and kill CD19+ B cells independent of MHC. Knockout of TRAC removes the endogenous TCR to reduce GvHD; HLA‑A/B and CIITA knockouts lower allorecognition and host rejection by minimizing MHC I/II expression; and PD‑1 knockout enhances resistance to checkpoint-mediated inhibition, improving antitumor activity against CD19+ malignancies.
NO
INDIRECT
Killing is triggered by recognition of CD19, not HLA-B. The engineered STAR T cells bind CD19 and induce perforin/granzyme-mediated cytolysis; HLA-B is knocked out on the therapeutic T cells to reduce allorecognition, not to kill HLA-B–expressing cells.
CRISPR-edited, healthy-donor T cells engineered with an anti-CD19 STAR receptor inserted at the TRAC locus and knockouts of TRAC, HLA-A/B, CIITA, and PD-1 to target CD19+ B cells while reducing rejection and GvHD.
Allogeneic CRISPR-edited donor T cells engineered with an anti‑CD19 STAR receptor inserted at the TRAC locus redirect TCR–CD3 signaling to recognize and kill CD19+ B cells independent of MHC. Knockout of TRAC removes the endogenous TCR to reduce GvHD; HLA‑A/B and CIITA knockouts lower allorecognition and host rejection by minimizing MHC I/II expression; and PD‑1 knockout enhances resistance to checkpoint-mediated inhibition, improving antitumor activity against CD19+ malignancies.
NO
INDIRECT
CIITA is not a cytotoxic target; it is knocked out in the donor T cells to reduce MHC II expression and allorecognition. Killing is directed at CD19+ cells via STAR receptor engagement, triggering TCR–CD3 signaling and cytolysis (perforin/granzymes/Fas pathways).