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 IgG1 kappa, isotype control [1] [2].
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 (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].
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].
References:
[1]. Sam J, et al. CD19-CD28: an affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy. Blood. 2024 May 23;143(21):2152-2165.
[2]. Sam J, et al. RG6333 (CD19-CD28), a CD19-targeted affinity-optimized CD28 bispecific antibody, enhances and prolongs the anti-tumor activity of glofitamab (CD20-TCB) in preclinical models. Blood 140.Supplement 1 (2022): 3142-3143.
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 (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].
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].
References:
[1]. Sam J, et al. CD19-CD28: an affinity-optimized CD28 agonist for combination with glofitamab (CD20-TCB) as off-the-shelf immunotherapy. Blood. 2024 May 23;143(21):2152-2165.
[2]. Sam J, et al. RG6333 (CD19-CD28), a CD19-targeted affinity-optimized CD28 bispecific antibody, enhances and prolongs the anti-tumor activity of glofitamab (CD20-TCB) in preclinical models. Blood 140.Supplement 1 (2022): 3142-3143.