2. Immunology/Inflammation
  3. Interleukin Related PD-1/PD-L1
  4. REGN-10597

REGN-10597, composed of an anti-huPD-1-targeting antibody and IL2Ra-IL2 moiety, is a PD-1-dependent IL-2 agonist. REGN-10597 binds PD-1 to deliver masked native IL-2 to PD-1+ T cells, engaging trimeric IL-2 receptors to activate downstream signaling. REGN-10597 can be used for the research on melanoma, prostate cancer, colorectal cancer, and ovarian cancer.

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REGN-10597 Related Antibodies

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Description

REGN-10597, composed of an anti-huPD-1-targeting antibody and IL2Ra-IL2 moiety, is a PD-1-dependent IL-2 agonist. REGN-10597 binds PD-1 to deliver masked native IL-2 to PD-1+ T cells, engaging trimeric IL-2 receptors to activate downstream signaling. REGN-10597 can be used for the research on melanoma, prostate cancer, colorectal cancer, and ovarian cancer[1][2][3].

Species Reactivity

Human
IC50 & Target[1]

IL-2

 

In Vitro

REGN-10597 (Serial dilutions; 30 min at 4°C) shows minimal binding to PD-1-knockout IL-2Rβ/γ+ and IL-2Rα/β/γ+ YT/STAT5-Luc reporter cells, with slightly enhanced binding to IL-2Rα-expressing cells[1].
REGN-10597 (4.5 h) exhibits PD-1-targeting-dependent IL-2 agonist activity in IL-2Rβ/γ+ YT/STAT5-Luc reporter cells, with enhanced potency correlating with increased PD-1 expression[1].
REGN-10597 (20 min) selectively enhances STAT5 phosphorylation in primary human PD-1+ CD8+ T cells compared to PD-1− CD8+ T cells, demonstrating PD-1-targeted IL-2 activity[1].
REGN-10597 (72 h) potently enhances primary human T cell activation in a mixed lymphocyte reaction[1].

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

REGN-10597 Related Antibodies
In Vivo

REGN-10597 (0.2 mg/kg; i.p.; single dose) induces initial tumor regression in 80% of MC38 tumor-bearing human PD-1 knockin mice, with 20% achieving durable complete tumor regression and long-term survival[1].
REGN-10597 (0.5 mg/kg; i.p.; every 3-4 days; 3 total doses)-mediated anti-tumor activity in MC38 tumor-bearing human PD-1 knockin mice is strictly dependent on CD8+ T cells, with pre-existing intratumoral CD8+ T cells playing a more significant role than newly recruited T cells[1].
REGN-10597 (0.5 mg/kg; i.p.) achieves 80% complete tumor regression and long-term survival in MC38 tumor-bearing human PD-1 knockin mice[1].
REGN-10597 (1.5 mg/kg; i.p.) induces significant tumor growth inhibition and 25% complete tumor regression in B16F10 melanoma-bearing human PD-1 knockin mice[1].
REGN-10597 (1.5 mg/kg; i.p.) induces significant tumor growth inhibition and 25% complete tumor regression in MCA205 fibrosarcoma-bearing human PD-1 knockin mice[1].
REGN-10597 treatment induces long-term anti-tumor memory, protecting MC38 tumor-cured human PD-1 knockin mice from tumor rechallenge[1].
REGN-10597 (0.5 mg/kg; i.p.; two doses on days 10 and 13 post-tumor engraftment) expands intratumoral PD-1+ CD8+ T cells with diverse effector and progenitor profiles, driving clonally expanded tumor-reactive T cell responses in MC38 tumor-bearing human PD-1 knockin mice[1].
REGN-10597 (0.5 mg/kg; i.p.; two doses on days 0 and 3) selectively expands PD-1+ CD8+ T cells in the peripheral blood of MC38 tumor-bearing human PD-1 knockin mice, demonstrating targeted activity[1].
REGN-10597 (1.8 mg/kg; i.p.; daily; 4 total doses) exhibits reduced systemic toxicity in healthy human PD-1 knockin mice, causing no significant body weight loss or pulmonary edema with daily dosing[1].

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

Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 0.2 mg/kg
Administration: i.p.; single dose
Result: Triggered efficient tumor growth control, with 8 out of 10 mice undergoing tumor regression within the first week of treatment.
Led to relapse in 6 out of 8 initial responders, leaving 2 out of 10 mice with complete tumor regression and long-term survival.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 0.5 mg/kg
Administration: i.p.; every 3-4 days; 3 total doses
Result: Had its tumor growth inhibition and tumor-free survival completely abrogated by depletion of CD8+ T cells.
Showed no effect change with depletion of CD4+ T cells or NK cells.
Retained most anti-tumor activity when T cell egress from lymph nodes was blocked with FTY720.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 0.5 mg/kg
Administration: i.p.
Result: Showed far superior potency in inhibiting tumor growth and improving tumor-free survival compared to non-targeting NT-IL2Ra-IL2, anti-PD-1 blocker, or their combination.
Led to 8 out of 10 mice achieving complete tumor regression and long-term survival.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 1.5 mg/kg
Administration: i.p.
Result: Significantly inhibited tumor growth, with 2 out of 8 mice achieving complete tumor regression.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 1.5 mg/kg
Administration: i.p.
Result: Significantly inhibited tumor growth, with 2 out of 8 mice achieving complete tumor regression.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 0.5 mg/kg
Administration: i.p.; two doses on days 10 and 13 post-tumor engraftment
Result: Led to pronounced expansion of intratumoral T cell populations, reducing myeloid populations.
Specifically expanded multiple PD-1+ CD8+ T cell clusters with robust effector gene expression (Gzma, Prf1, Ifng), proliferative activity, and clonal expansion indicative of tumor antigen recognition.
Enriched a subset of stem-like progenitor CD8+ T cells (TCF1+ PD-1+).
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 0.5 mg/kg
Administration: i.p.; two doses on days 0 and 3
Result: Led to selective expansion of PD-1+ CD8+ T cells in peripheral blood, with minimal effect on PD-1- CD8+ T cells.
Animal Model: Human PD-1 knockin mice (female, 8-16 weeks old)[2]
Dosage: 1.8 mg/kg
Administration: i.p.; daily; 4 total doses
Result: Did not result in significant body weight loss or increased pulmonary wet weight (a marker of pulmonary edema), indicating reduced systemic toxicity compared to unmasked IL-2 molecules.
Gene ID

5133  [NCBI]

Accession
Target

PDCD1/PD-1/CD279
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.
Formulation

Please refer to the lot-specific COA for specific buffer information.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Format
  • anti-PD-1/IL-2Ra/IL-2 fusion protein
Purity & Documentation
References
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REGN-10597 Related Classifications

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Help & FAQs
  • 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.

Keywords:

REGN-10597REGN10597REGN 10597Interleukin RelatedPD-1/PD-L1ILPD-1/Programmed death-ligand 1fibrosarcomacolorectal cancerIL-2Rβtumor microenvironmentIL-2RγPD-1+ CD8+ T cellsmelanomaprostate cancerPD-1IL-2RαInhibitorinhibitorinhibit

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