InVivoMAb anti-human GPC-2
Product Description
Specifications
| Isotype | Mouse IgG1, κ |
|---|---|
| Recommended Isotype Control(s) | InVivoMAb mouse IgG1 isotype control, unknown specificity |
| Recommended Dilution Buffer | InVivoPure pH 7.0 Dilution Buffer |
| Conjugation | This product is unconjugated. Conjugation is available via our Antibody Conjugation Services. |
| Immunogen | KLH conjugated synthetic peptide corresponding to the C-terminal residues 504-553 of human GPC2 |
| Reported Applications |
Immunohistochemistry (paraffin) Flow cytometry ELISA Western blot |
| Formulation |
PBS, pH 7.0 Contains no stabilizers or preservatives |
| Endotoxin |
≤1EU/mg (≤0.001EU/μg) Determined by LAL assay |
| Purity |
≥95% Determined by SDS-PAGE |
| Sterility | 0.2 µm filtration |
| Production | Purified from cell culture supernatant in an animal-free facility |
| Purification | Protein G |
| Molecular Weight | 150 kDa |
| Storage | The antibody solution should be stored at the stock concentration at 4°C. Do not freeze. |
| Need a Custom Formulation? | See All Antibody Customization Options |
Application References
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Sun M, Cao Y, Okada R, Reyes-González JM, Stack HG, Qin H, Li N, Seibert C, Kelly MC, Ruppin E, Ho M, Thiele CJ, Nguyen R (2023). "Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma" J Immunother Cancer 11(1):e005881.
PubMed
Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods: We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results: Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8+ effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY, GZMB, ZNF683, and HMGN2. Finally, we also showed that the CT3.28H.BBζ CAR we developed was more potent than a recently clinically tested GD2-targeted CAR to control NB growth in vivo. Conclusion: Given the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.
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Sun M, Cao Y, Okada R, Reyes-González JM, Stack HG, Qin H, Li N, Seibert C, Kelly MC, Ruppin E, Ho M, Thiele CJ, Nguyen R (2023). "Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma" J Immunother Cancer 11(1):e005881.
PubMed
Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods: We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results: Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8+ effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY, GZMB, ZNF683, and HMGN2. Finally, we also showed that the CT3.28H.BBζ CAR we developed was more potent than a recently clinically tested GD2-targeted CAR to control NB growth in vivo. Conclusion: Given the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.
-
Sun M, Cao Y, Okada R, Reyes-González JM, Stack HG, Qin H, Li N, Seibert C, Kelly MC, Ruppin E, Ho M, Thiele CJ, Nguyen R (2023). "Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma" J Immunother Cancer 11(1):e005881.
PubMed
Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods: We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results: Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8+ effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY, GZMB, ZNF683, and HMGN2. Finally, we also showed that the CT3.28H.BBζ CAR we developed was more potent than a recently clinically tested GD2-targeted CAR to control NB growth in vivo. Conclusion: Given the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.
-
Sun M, Cao Y, Okada R, Reyes-González JM, Stack HG, Qin H, Li N, Seibert C, Kelly MC, Ruppin E, Ho M, Thiele CJ, Nguyen R (2023). "Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma" J Immunother Cancer 11(1):e005881.
PubMed
Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods: We evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results: Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8+ effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY, GZMB, ZNF683, and HMGN2. Finally, we also showed that the CT3.28H.BBζ CAR we developed was more potent than a recently clinically tested GD2-targeted CAR to control NB growth in vivo. Conclusion: Given the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.
Product Citations
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GPC2-Targeted CAR T Cells Engineered with NFAT-Inducible Membrane-Tethered IL15/IL21 Exhibit Enhanced Activity against Neuroblastoma.
In Cancer Immunol Res on 2 September 2025 by Okada, R., Reyes-González, J. M., et al.
PubMed
Neuroblastoma is a highly aggressive childhood solid tumor with poor outcomes. Chimeric antigen receptor (CAR) T cells have shown limited efficacy in neuroblastoma, with the best outcomes reported in patients with a low tumor burden, highlighting the need for further CAR optimization. One approach to addressing the high tumor burden involves engineering CAR T cells to release or express transgenic cytokines. However, its systemic toxicity remains an important therapeutic challenge. In this study, we evaluated the efficacy of IL15- and IL21-enhanced glypican 2 (GPC2)-targeted CAR T cells (GPC2-CAR T cells) in targeting high-burden neuroblastoma. Three strategies for expressing the cytokines were evaluated: constitutive secretion (GPC2-CAR + sol.IL15.IL21), constitutive membrane-tethered expression (GPC2-CAR + teth.IL15.IL21), and NFAT-inducible membrane-tethered expression (GPC2-CAR + NFAT.IL15.IL21). Engineered GPC2-CAR T cells were tested in vitro and in vivo using high neuroblastoma burden xenograft models. Additionally, single-cell RNA sequencing was used to profile the effector cells in the tumor microenvironment. All three versions of GPC2-CAR T cells significantly enhanced killing against a high neuroblastoma burden, both in vitro and in vivo, relative to control GPC2-CAR T cells. Mice treated with GPC2-CAR + NFAT.IL15.IL21 exhibited significantly lower anorexia-associated morbidity/mortality. Supporting these data, tumor-infiltrating GPC2-CAR + NFAT.IL15.IL21 developed an immunosuppressive transcriptional profile upon tumor regression, leading to prolonged survival in treated mice. In contrast, GPC2-CAR + teth.IL15.IL21 maintained a proinflammatory transcriptional signature despite near tumor clearance, resulting in hypercytokinemia and death. NFAT-inducible co-expression of tethered IL15/IL21 enhanced GPC2-CAR T-cell function against a high neuroblastoma burden with acceptable tolerability in mice. Further studies are required to validate these findings.