bioRxiv : the preprint server for biologyMay 7, 2026

Gene-edited immune cells from donors show strong cancer-fighting effects in solid tumors

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Off-the-shelf CRISPR-engineered CAR-T cells targeting GPC2 or GPC3 showed strong antitumor activity in solid tumor models.

Evidence

This preclinical platform experiment tested genome-edited allogeneic CAR-T cells in multiple in vitro and in vivo neuroblastoma and hepatocellular carcinoma models.

Caveat

The evidence is limited to preclinical tumor models, so human efficacy, durability, dosing, and safety remain untested.

Simplified

Chimeric antigen receptor (CAR) T-cell therapy has shown limited efficacy in solid tumors, in part due to variability in autologous T cells derived from heavily pretreated patients with advanced disease. To address these constraints, we developed an off-the-shelf allogeneic CAR-T platform using CRISPR-Cas9-mediated genome editing in T cells from healthy donors to enable targeted CAR insertion at thelocus with concurrent disruption of. Using adeno-associated virus (AAV) delivery, we designed CAR-T cells targeting glypican-2 (GPC2) and glypican-3 (GPC3), emerging antigens expressed in pediatric and adult solid tumors. Genome-edited allogeneic CAR-T cells exhibited potent, antigen-specific cytotoxicity across multiple tumor models. GPC2-directed allogeneic CAR-T cells demonstrated enhanced or comparable activity relative to conventional lentiviral CAR-T cells in neuroblastoma models and mediated tumor regression with prolonged survival in preclinical models. Notably, repeated dosing augmented antitumor efficacy without evidence of toxicity, supporting multi-dose regimens for solid tumors. Similarly, GPC3-targeted allogeneic CAR-T cells based on a single-domain antibody showed robust activity against hepatocellular carcinoma cells in vitro and in vivo. These findings establish a scalable, genome-engineered allogeneic CAR-T strategy with strong therapeutic potential and support the clinical development of off-the-shelf cell therapies for pediatric and adult solid tumors. TRAC B2M

Funding

Competing interests

Declaration of interest statement M.Ho, D.L. and N.L. have patents related to antibody and cell-based immunotherapies targeting GPC2 or GPC3 and may receive blind royalties from the NIH. M.Ho received research funds from CRISPR Therapeutics via Cooperative Research and Development Agreement (CRADA) assigned to the NIH. D.H., J.S., M.P., L.H., K.M., and M.E. are employees of CRISPR Therapeutics. The authors declare no other conflicts of interest.

PubMed