Journal: bioRxiv

Article Title: Synthetic Hybrid Receptors for Safer and Programmable T Cell Therapy

doi: 10.64898/2026.01.22.701150

Figure Lengend Snippet: a , Schematic of one-site viral Hybrid-R targeting strategy. b , BFP reporter expression in Hybrid-R knock-in primary human T cells 72 hours after stimulation with B7-H3 + A375 target cells. c , Quantification (MFI) of BFP reporter expression after 72 hours with B7-H3 + A549 target cells. (data from 2 independent donors n=3). d , Relative target cell lysis by anti-B7-H3 Hybrid-Rs targeting B7-H3 + MES-SAmKate-NLS cells measured by Incucyte live-cell imaging. Effector to target ratio is 1:4. Data are total area normalized to TRAC knockout T cells (n=3 technical replicates). e , Schematic of one-site non-viral Hybrid-R targeting strategy. f , Contour plots depict antigen dependent induction of BFP reporter in Hybrid-R T cells in response to 72 hours stimulation with B7-H3 + MES-SA target cells. Representitive of 2 biological replicates. g , Quantification (MFI) of BFP reporter expression (n=2 biological replicates). Statistics calculated with one-way ANOVA with Šídák’s multiple comparisons test. Mean SEM is depicted. h , Schematic of one-site non-viral targeting strategy. i , Schematic of in vivo study. j , Tumor volumes from B7-H3 + MES-SA tumor-bearing animals treated with 1.0e6 engineered T cells 8 days after tumor innoculation. Lines indicate individual mice. Tumor volume statistics analyzed using one-way ANOVA with Dunnett’s correction comparing the area under the curve versus the control group over the course of the experiment.

Article Snippet: The cancer cell lines used were K562 (originating from female myelogenous leukemia cells) (ATCC), A549 (originating from male, lung epithelial carcinoma cells) (ATCC), A375 malignant melanoma (originally obtained from Dr. Alexander Marson’s laboratory at UCSF, originating from female melanoma cells), M28 human epithelioid cells (originally obtained from Dr. Brenda Gerwin’s laboratory at the National Cancer Institute), MES-SA (uterine sarcoma) (ATCC), and B16-F10 melanoma cells (ATCC).

Techniques: Expressing, Knock-In, Lysis, Live Cell Imaging, Knock-Out, In Vivo, Control

Journal: bioRxiv

Article Title: Synthetic Hybrid Receptors for Safer and Programmable T Cell Therapy

doi: 10.64898/2026.01.22.701150

Figure Lengend Snippet: a , Schematic of GMP compatible manufacturing strategy. b , Schematic of one-site non-viral targeting strategy. c , Relative target cell lysis by anti-B7-H3 Hybrid-Rs targeting B7-H3 + MES-SAmKate-NLS cells measured by Incucyte live-cell imaging. Effector to target ratio is 1:8. Data are total area normalized to first timepoint (n=3 technical replicates). d , Normalized T cell counts after 48 hours incubation with AP20187 (n=2 technical replicates). e , Schematic of in vivo study. f , Tumor volumes from B7-H3 + MES-SA tumor-bearing NSG animals treated with engineered T cells 5 days after tumor innoculation. Lines indicate individual mice.Tumor volume statistics analyzed using one-way ANOVA with Dunnett’s correction comparing the area under the curve versus the control group over the course of the experiment. g , Survival of B7-H3 + MES-SA tumor bearing NSG animals. P values calculated using log-rank Mantel-Cox (survival).

Article Snippet: The cancer cell lines used were K562 (originating from female myelogenous leukemia cells) (ATCC), A549 (originating from male, lung epithelial carcinoma cells) (ATCC), A375 malignant melanoma (originally obtained from Dr. Alexander Marson’s laboratory at UCSF, originating from female melanoma cells), M28 human epithelioid cells (originally obtained from Dr. Brenda Gerwin’s laboratory at the National Cancer Institute), MES-SA (uterine sarcoma) (ATCC), and B16-F10 melanoma cells (ATCC).

Techniques: Lysis, Live Cell Imaging, Incubation, In Vivo, Control