Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Expression profiles of TROP2 and c-Met in tumor and normal tissues (A) TROP2 gene expression profile in pancreatic tumor and normal tissues in humans. See also . (B) MET gene expression profile in pancreatic tumor and normal tissues in humans based on data from GEPIA (Gene Expression Profiling Interactive Analysis). (C) Comparative analysis of TROP2 and MET gene expression in tumor tissues and normal tissues in pancreatic cancer (PAAD), lung adenocarcinoma (LUAD), and colon cancer (COAD) patients. See also . (D) Overall survival analysis of patients with high versus low TROP2 or MET gene expression. (E) Multicolor fluorescence tissue microarray analysis of TROP2 and c-Met protein expression in tumor tissues from 55 clinical patients (spanning seven cancer types) and normal tissues. Quantitative fluorescence analysis was performed, with TROP2 shown in red and c-Met shown in green. (F) Quantitative fluorescence distribution of TROP2 and c-Met protein expression from (E). (G) Representative multicolor fluorescence images of tissue microarrays from PAAD, LUAD, and COAD patients, showing TROP2 (red), c-Met (green), and nuclei (blue, DAPI). Scale bars, 200 μm and 100 μm. See also . (H) Flow cytometry analysis of TROP2 and c-Met expression in representative cell lines derived from different cancer types, including BxPC-3, NCI-H358, SPC-A1, MDA-MB-231, and HT-29 ( n = 3 independent experiments). See also .

Article Snippet: TROP2 and c-Met expression profiles in patients with tumors versus healthy controls , HPA (The Human Protein Atlas) , HPA:https://www.proteinatlas.org/search/tacstd2,; https://www.proteinatlas.org/search/MET.

Techniques: Expressing, Gene Expression, Fluorescence, Microarray, Flow Cytometry, Derivative Assay

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Development and characterization of nanobody-based BsADCs (A) Structural design of four bispecific antibodies targeting TROP2 and c-Met (created with BioRender.com ). (B) Schematic representation of the B6ADC structure. (C) Determination of the DAR of reduced B6ADC single chains via LC-MS ( n = 3 independent experiments). (D) Binding affinities of B6HCAb and B6ADC for the TROP2 and c-Met proteins, measured by Biacore 8K ( n = 3 independent experiments). (E) Schematic and results validating the ability of the B6HCAb-1 to simultaneously bind TROP2 and c-Met antigens ( n = 3 independent experiments). Scale bar, 10 μm. (F) AlphaFold3-predicted key hydrogen bonding interaction sites between the TROP2 VHH and TROP2 proteins ( n = 3 independent experiments). See also . (G) AlphaFold3-predicted key hydrogen bonding interaction sites between the c-Met VHH and the c-Met protein ( n = 3 independent experiments). See also . (H) Binding capacity of B6HCAb to TROP2 antigen and its variants ( n = 2∼3/group). (I) Binding capacity of B6HCAb to c-Met antigen and its variants ( n = 2∼3/group). See also .

Article Snippet: TROP2 and c-Met expression profiles in patients with tumors versus healthy controls , HPA (The Human Protein Atlas) , HPA:https://www.proteinatlas.org/search/tacstd2,; https://www.proteinatlas.org/search/MET.

Techniques: Liquid Chromatography with Mass Spectroscopy, Binding Assay

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Validation of the mechanism and cytotoxicity of B6ADC (A and B) Colocalization of B6ADC with lysosomes. B6ADC is shown in red, lysosomes are shown in green, and nuclei are shown in blue (DAPI) ( n = 3 independent experiments). Scale bars, 20 μm and 10 μm. (C and D) Penetration ability of B6ADC and parental ADCs in BxPC-3 tumor spheroids. B6ADC is shown in red, and nuclei are shown in blue (DAPI) ( n = 3 independent experiments). Scale bar, 100 μm. See also . (E) Cytotoxicity of B6ADC and parental ADCs, including BxPC-3, NCI-H358, SPC-A1, MDA-MB-231, HT-29, and OVCAR-3, in various tumor cell lines with different TROP2/c-Met expression levels ( n = 3/group). See also and . (F) Cytotoxicity of B6ADC to normal human cells (HUVECs and MRC-5 cells) ( n = 3/group). (G) Tumor spheroid lysis ability of B6ADC and parental ADCs in BxPC-3 tumor spheroids ( n = 3 independent experiments). Scale bar, 100 μm. Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗ p < 0.05, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, and p > 0.05 (no significance, ns).

Article Snippet: TROP2 and c-Met expression profiles in patients with tumors versus healthy controls , HPA (The Human Protein Atlas) , HPA:https://www.proteinatlas.org/search/tacstd2,; https://www.proteinatlas.org/search/MET.

Techniques: Biomarker Discovery, Expressing, Lysis

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Broad-spectrum antitumor activity of B6ADC (A) Tumor suppression efficacy of B6ADC in multiple pancreatic cancer CDX models ( n = 5∼7/group). (B) Tumor suppression efficacy of B6ADC in four cell lines with varying TROP2/c-Met expression levels ( n = 5∼7/group). Scale bar, 50 μm. (C) Tumor suppression effect of a single 2.2 mg/kg dose of B6ADC in SPC-A1 lung adenocarcinoma-bearing mice with a tumor volume of 1,200 mm 3 ( n = 5∼7/group). (D) Comparison of tumor suppression between B6ADC and the combination of parental “TROP2ADC and c-MetADC” in SPC-A1 tumor-bearing mice (initial tumor volume: 600 mm 3 ) ( n = 6/group). See also . (E) Comparison of tumor suppression between B6ADC and the combination of “marketed TROP2ADC (SG) and marketed c-MetADC (Teliso-V)” in SPC-A1 tumor-bearing mice (initial tumor volume: 600 mm 3 ) ( n = 5∼7/group). See also . (F) Transmission electron microscopy images showing apoptosis in BxPC-3 tumors on day 7 after treatment with B6ADC and the control. Apoptotic features (e.g., chromatin condensation and nuclear fragmentation) were observed in the B6ADC-treated group ( n = 3 independent experiments). Scale bar, 2 μm. See also . Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗ p < 0.05, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, and p > 0.05 (no significance, ns).

Article Snippet: TROP2 and c-Met expression profiles in patients with tumors versus healthy controls , HPA (The Human Protein Atlas) , HPA:https://www.proteinatlas.org/search/tacstd2,; https://www.proteinatlas.org/search/MET.

Techniques: Activity Assay, Expressing, Comparison, Transmission Assay, Electron Microscopy, Control

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Safety and pharmacokinetics of B6ADC (A) Body weight changes in BALB/c mice treated with B6ADC at doses of 44 mg/kg, 66 mg/kg, and 110 mg/kg ( n = 4∼6/group). See also . (B) Dose-dependent safety evaluation of B6ADC in TROP2-humanized mice and c-Met-humanized mice ( n = 4/group). (C) Biochemical analysis of liver function (AST, ALT, and T-Bil) and kidney function (Cr and BUN) in TROP2-humanized mice and c-Met-humanized mice ( n = 4/group). (D) MMAE release level of B6ADC in BALB/c mice ( n = 5/group). (E) MMAE release in tumor tissues, serum, and major organs (heart, liver, spleen, lung, and kidney) at different time points after the administration of 2.2 mg/kg B6ADC to BALB/c mice ( n = 3/group). Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗∗∗∗ p < 0.0001.

Article Snippet: TROP2 and c-Met expression profiles in patients with tumors versus healthy controls , HPA (The Human Protein Atlas) , HPA:https://www.proteinatlas.org/search/tacstd2,; https://www.proteinatlas.org/search/MET.

Techniques: Drug discovery

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Expression profiles of TROP2 and c-Met in tumor and normal tissues (A) TROP2 gene expression profile in pancreatic tumor and normal tissues in humans. See also . (B) MET gene expression profile in pancreatic tumor and normal tissues in humans based on data from GEPIA (Gene Expression Profiling Interactive Analysis). (C) Comparative analysis of TROP2 and MET gene expression in tumor tissues and normal tissues in pancreatic cancer (PAAD), lung adenocarcinoma (LUAD), and colon cancer (COAD) patients. See also . (D) Overall survival analysis of patients with high versus low TROP2 or MET gene expression. (E) Multicolor fluorescence tissue microarray analysis of TROP2 and c-Met protein expression in tumor tissues from 55 clinical patients (spanning seven cancer types) and normal tissues. Quantitative fluorescence analysis was performed, with TROP2 shown in red and c-Met shown in green. (F) Quantitative fluorescence distribution of TROP2 and c-Met protein expression from (E). (G) Representative multicolor fluorescence images of tissue microarrays from PAAD, LUAD, and COAD patients, showing TROP2 (red), c-Met (green), and nuclei (blue, DAPI). Scale bars, 200 μm and 100 μm. See also . (H) Flow cytometry analysis of TROP2 and c-Met expression in representative cell lines derived from different cancer types, including BxPC-3, NCI-H358, SPC-A1, MDA-MB-231, and HT-29 ( n = 3 independent experiments). See also .

Article Snippet: c-Met (Cytoplasmic) Polyclonal antibody , Wuhan Sanying , Cat#25869-1-AP; RRID: AB_2880276.

Techniques: Expressing, Gene Expression, Fluorescence, Microarray, Flow Cytometry, Derivative Assay

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Development and characterization of nanobody-based BsADCs (A) Structural design of four bispecific antibodies targeting TROP2 and c-Met (created with BioRender.com ). (B) Schematic representation of the B6ADC structure. (C) Determination of the DAR of reduced B6ADC single chains via LC-MS ( n = 3 independent experiments). (D) Binding affinities of B6HCAb and B6ADC for the TROP2 and c-Met proteins, measured by Biacore 8K ( n = 3 independent experiments). (E) Schematic and results validating the ability of the B6HCAb-1 to simultaneously bind TROP2 and c-Met antigens ( n = 3 independent experiments). Scale bar, 10 μm. (F) AlphaFold3-predicted key hydrogen bonding interaction sites between the TROP2 VHH and TROP2 proteins ( n = 3 independent experiments). See also . (G) AlphaFold3-predicted key hydrogen bonding interaction sites between the c-Met VHH and the c-Met protein ( n = 3 independent experiments). See also . (H) Binding capacity of B6HCAb to TROP2 antigen and its variants ( n = 2∼3/group). (I) Binding capacity of B6HCAb to c-Met antigen and its variants ( n = 2∼3/group). See also .

Article Snippet: c-Met (Cytoplasmic) Polyclonal antibody , Wuhan Sanying , Cat#25869-1-AP; RRID: AB_2880276.

Techniques: Liquid Chromatography with Mass Spectroscopy, Binding Assay

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Validation of the mechanism and cytotoxicity of B6ADC (A and B) Colocalization of B6ADC with lysosomes. B6ADC is shown in red, lysosomes are shown in green, and nuclei are shown in blue (DAPI) ( n = 3 independent experiments). Scale bars, 20 μm and 10 μm. (C and D) Penetration ability of B6ADC and parental ADCs in BxPC-3 tumor spheroids. B6ADC is shown in red, and nuclei are shown in blue (DAPI) ( n = 3 independent experiments). Scale bar, 100 μm. See also . (E) Cytotoxicity of B6ADC and parental ADCs, including BxPC-3, NCI-H358, SPC-A1, MDA-MB-231, HT-29, and OVCAR-3, in various tumor cell lines with different TROP2/c-Met expression levels ( n = 3/group). See also and . (F) Cytotoxicity of B6ADC to normal human cells (HUVECs and MRC-5 cells) ( n = 3/group). (G) Tumor spheroid lysis ability of B6ADC and parental ADCs in BxPC-3 tumor spheroids ( n = 3 independent experiments). Scale bar, 100 μm. Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗ p < 0.05, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, and p > 0.05 (no significance, ns).

Article Snippet: c-Met (Cytoplasmic) Polyclonal antibody , Wuhan Sanying , Cat#25869-1-AP; RRID: AB_2880276.

Techniques: Biomarker Discovery, Expressing, Lysis

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Broad-spectrum antitumor activity of B6ADC (A) Tumor suppression efficacy of B6ADC in multiple pancreatic cancer CDX models ( n = 5∼7/group). (B) Tumor suppression efficacy of B6ADC in four cell lines with varying TROP2/c-Met expression levels ( n = 5∼7/group). Scale bar, 50 μm. (C) Tumor suppression effect of a single 2.2 mg/kg dose of B6ADC in SPC-A1 lung adenocarcinoma-bearing mice with a tumor volume of 1,200 mm 3 ( n = 5∼7/group). (D) Comparison of tumor suppression between B6ADC and the combination of parental “TROP2ADC and c-MetADC” in SPC-A1 tumor-bearing mice (initial tumor volume: 600 mm 3 ) ( n = 6/group). See also . (E) Comparison of tumor suppression between B6ADC and the combination of “marketed TROP2ADC (SG) and marketed c-MetADC (Teliso-V)” in SPC-A1 tumor-bearing mice (initial tumor volume: 600 mm 3 ) ( n = 5∼7/group). See also . (F) Transmission electron microscopy images showing apoptosis in BxPC-3 tumors on day 7 after treatment with B6ADC and the control. Apoptotic features (e.g., chromatin condensation and nuclear fragmentation) were observed in the B6ADC-treated group ( n = 3 independent experiments). Scale bar, 2 μm. See also . Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗ p < 0.05, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001, and p > 0.05 (no significance, ns).

Article Snippet: c-Met (Cytoplasmic) Polyclonal antibody , Wuhan Sanying , Cat#25869-1-AP; RRID: AB_2880276.

Techniques: Activity Assay, Expressing, Comparison, Transmission Assay, Electron Microscopy, Control

Journal: Cell Reports Medicine

Article Title: A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer

doi: 10.1016/j.xcrm.2026.102688

Figure Lengend Snippet: Safety and pharmacokinetics of B6ADC (A) Body weight changes in BALB/c mice treated with B6ADC at doses of 44 mg/kg, 66 mg/kg, and 110 mg/kg ( n = 4∼6/group). See also . (B) Dose-dependent safety evaluation of B6ADC in TROP2-humanized mice and c-Met-humanized mice ( n = 4/group). (C) Biochemical analysis of liver function (AST, ALT, and T-Bil) and kidney function (Cr and BUN) in TROP2-humanized mice and c-Met-humanized mice ( n = 4/group). (D) MMAE release level of B6ADC in BALB/c mice ( n = 5/group). (E) MMAE release in tumor tissues, serum, and major organs (heart, liver, spleen, lung, and kidney) at different time points after the administration of 2.2 mg/kg B6ADC to BALB/c mice ( n = 3/group). Statistical analysis was performed using two-way ANOVA. The data are presented as the means ± SDs. ∗∗∗∗ p < 0.0001.

Article Snippet: c-Met (Cytoplasmic) Polyclonal antibody , Wuhan Sanying , Cat#25869-1-AP; RRID: AB_2880276.

Techniques: Drug discovery