1. Immunology/Inflammation
  2. CD19 CD28
  3. RG-6333

RG-6333 is a bispecific agonist targeting CD19 and CD28. RG-6333 specifically recognizes and binds to the CD19 antigen on the surface of B-cell malignancies to locate tumor cells. RG-6333 activates T cells by binding to CD28, overcoming activation barriers to enhance anti-tumor immunity. RG-6333 can be used in the study of relapsed/refractory non-Hodgkin's lymphoma. The recommended isotype control is human IgG4 kappa, isotype control (HY-P99003).

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RG-6333 Chemical Structure

RG-6333 Chemical Structure

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Description

RG-6333 is a bispecific agonist targeting CD19 and CD28. RG-6333 specifically recognizes and binds to the CD19 antigen on the surface of B-cell malignancies to locate tumor cells. RG-6333 activates T cells by binding to CD28, overcoming activation barriers to enhance anti-tumor immunity. RG-6333 can be used in the study of relapsed/refractory non-Hodgkin's lymphoma. The recommended isotype control is human IgG4 kappa, isotype control (HY-P99003)[1][2].

In Vitro

RG-6333 (RO 7443904) has a lower affinity for CD28 in CHO cells (Kd: 36 nM), binding weakly but sufficient to provide a co-stimulatory signal[1].
RG-6333 is inactive as a single agent in human peripheral blood mononuclear cells (PBMC) and activates T cells only upon engagement of the T cell receptor (TCR)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

RG-6333 (1,10 mg/kg, i.v. one dose) activates T cells only in the presence of T cell receptor (TCR) signaling in humanized NSG mice and does not induce a cytokine storm[1][2].
RG-6333 (1 mg/kg, i.v. one dose) significantly inhibits tumor growth in humanized NSG mice bearing subcutaneous NALM-6 lymphoma in combination with Glofitamab (HY-P99024) (0.15 mg/kg), and increases tumor-infiltrating CD8+ T cells[1].
RG-6333 (1 mg/kg, i.v. one dose) combines with Glofitamab (0.15 mg/kg) in an aggressive in vivo lymphoma (DLBCL WSU-DLCL2-Fluc) humanized mice model results in complete tumor regression, with an initial transient weight loss due to T cell activation, but subsequent recovery[1][2].
RG-6333 (1 mg/kg, i.v. one dose) combines with glofitamab (0.15 mg/kg) in a humanized NSG mice model bearing subcutaneous OCI-Ly18 tumors increases pro-inflammatory T cell signatures in tumors and promotes transendothelial migration, and triple combination with CD19–4-1BBL deepens and prolongs anti-tumor responses in vivo[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Humanized NSG mice bearing orthotopic WSU-DLCL2-Fluc tumors[1]
Dosage: 1 mg/kg
Administration: i.v. three times combined injection
Result: Combined with Glofitamab (0.15 mg/kg) achieved complete tumor regression, with initial weight loss in mice, which is related to the mode of action of TCB and its induced cytokine release.
Combined with Glofitamab (0.15 mg/kg) led to subsequent recovery of mice without additional weight loss suggestive of tumor progression, indicated potent antitumor activity.
Animal Model: OCI-Ly18 tumor-bearing humanized NSG mice[1]
Dosage: 1 mg/kg
Administration: i.v. three times combined injection
Result: Combined with Glofitamab (1 mg/kg) increased intratumoral CD8+ and CD4+ T-cell counts.
Combined with Glofitamab (1 mg/kg) led to a marked increase in IFNγ pathway genes, followed by significantly increased cytotoxic T-cell and decreased B-cell signatures.
Combined with Glofitamab (1 mg/kg) and CD19-4-1BBL (1 mg/kg) prolonged the anti-tumor response in vivo and achieving long-term tumor control.
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[RG-6333]

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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RG-6333
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HY-P991176
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