Anti-Mouse CD309 (VEGFR2) [Clone DC101] — Purified in vivo PLATINUM™ Functional Grade

Clone DC101 is most commonly used in vivo in mice to block signaling through vascular endothelial growth factor receptor 2 (VEGFR-2, also known as CD309/Flk-1/KDR), thereby inhibiting angiogenesis and suppressing tumor growth.

Essential applications in vivo include:

• Inhibition of angiogenesis: DC101 is widely used to block VEGFR-2-mediated pathways, preventing the formation of new blood vessels essential for tumor growth and metastasis.
• Tumor growth suppression: By impairing tumor vasculature, DC101 reduces the growth and proliferation of various tumor types in mouse models.
• Assessment of VEGF/VEGFR-2 pathway involvement: Researchers use DC101 to probe the role of VEGFR-2 in physiological and pathological processes involving vascular development and permeability.
• Therapeutic efficacy studies: DC101 serves as a reference or therapeutic tool in preclinical studies testing anti-angiogenic strategies for cancer treatment. For example, administration of DC101 in mice bearing solid tumors leads to significant inhibition of tumor growth relative to controls.
• Immune therapy investigations: DC101, or engineered versions such as DC101-CAR T cells, have been used to target tumor vasculature and enhance immune responses against tumors in vivo.

Other reported but less common in vivo applications:

• Blockade of VEGFR-2 signaling in models of ocular neovascularization or inflammatory diseases.
• Investigation of tissue-specific roles of angiogenesis in development, wound healing, or organ homeostasis.

Application formats:
DC101 is typically administered as a purified rat IgG1 monoclonal antibody for systemic blocking of murine VEGFR-2 function in live mice.

Summary table:

DC101 is not used for immunohistochemistry or direct detection of VEGFR-2 in tissues in vivo but is instead employed for functional blockade or as a targeting moiety in modified therapeutic approaches.

Commonly used antibodies or proteins combined with DC101 (an anti-VEGFR2 antibody) in the literature include:

• Anti-VEGF-A antibodies (e.g., clone 2G11-2A05): Frequently employed to achieve dual blockade of VEGF-A and VEGFR2, examining the enhanced effect on inhibition of tumor angiogenesis and growth.
• Cetuximab (anti-EGFR): Used in combination with DC101 to study synergistic anti-tumor and anti-metastatic effects, particularly in squamous cell carcinoma and other tumor types.
• VEGF-Trap (Aflibercept): Compared against DC101 in preclinical studies as an alternative VEGF blocking agent; while not usually used in combination, it's evaluated in similar settings for comparative efficacy.

Additional proteins or markers used in mechanistic or histological studies with DC101:

• CD31: An endothelial cell marker, commonly used in immunohistochemistry to quantify microvessel density in tumors treated with DC101 (assessing anti-angiogenic effects).
• PCNA (Proliferating Cell Nuclear Antigen): Used to assess tumor cell proliferation after DC101 treatment.
• TUNEL assay: Applied to measure apoptosis levels in tissue sections exposed to DC101.
• Vinblastine: A chemotherapeutic agent used in combination with DC101 to assess additive or synergistic anti-tumor effects in vivo.

These combinations are designed to either enhance anti-angiogenic effect, test dual pathway inhibition, or assess impact on related biological markers in tumor models.

Key findings from scientific literature citing clone DC101 focus on its role as a monoclonal antibody that targets VEGFR-2 (vascular endothelial growth factor receptor 2), resulting in significant antiangiogenic and antitumor effects.

Essential findings include:

• Inhibition of Tumor Angiogenesis and Growth:
  DC101 effectively blocks VEGFR-2, leading to rapid and substantial reduction in tumor blood vessel formation and tumor growth in vivo. Beginning as early as 24 hours post-treatment, studies report a marked decrease in vessel density, reduced endothelial cell proliferation, and areas of tumor necrosis due to diminished vascular supply.

• Rapid Vessel Regression and Stromal Changes:
  DC101 treatment induces rapid regression of pre-existing vessels within the tumor stroma. This is accompanied by decreased expression of stromal matrix metalloproteinases (MMP-9 and MMP-13), changes in tumor-stroma border morphology, and in some cases, reversion of an invasive tumor phenotype to a well-demarcated, premalignant state.

• Modulation of Tumor Microenvironment:
  Beyond vascular effects, DC101-modified CAR T cells show enhanced persistence within tumors, indicating activity against VEGFR-2–expressing tumor vasculature and suggesting potent immune modulation. Treatment with DC101 also stimulates the formation of high endothelial venules in the tumor, supporting immune cell infiltration.

• Synergy with Combination Therapies:
  Combining DC101-mediated VEGFR-2 inhibition with other treatments (including anti–VEGFR-1 antibodies, chemotherapy, and immunotherapy) results in enhanced antitumor effects compared to monotherapy.

• Impact on Host Physiology:
  Blockade of VEGFR-2 by DC101 can cause systemic effects such as hypertension, likely by reducing nitric oxide (NO) production, highlighting potential side effects to consider in translational approaches.

In summary, clone DC101 is widely cited for its robust antiangiogenic effects via VEGFR-2 inhibition, its capacity to modulate the tumor microenvironment, and its utility in combination therapeutic strategies, all of which underpin its importance as a tool in cancer research and preclinical therapy development.

Dosing regimens of DC101—a monoclonal antibody targeting mouse VEGFR-2—vary considerably across mouse models depending on tumor type, experimental aim (e.g., antiangiogenesis, immune response modulation), and combination with other treatments.

Key regimens and model differences:

• Leukemia models (NOD-SCID mice): 800 μg/injection, intraperitoneally (i.p.), three times per week.
• Breast cancer models (MCaP0008): Doses of 10, 20, or 40 mg/kg body weight, administered at 3-day intervals; low-dose regimens (10 or 20 mg/kg) showed unique vascular and immune effects different from high-dose (40 mg/kg).
• Colorectal tumor models (MC38 mice): 5, 20, or 40 mg/kg i.p.; mid (20 mg/kg) and high (40 mg/kg) doses led to significant tumor growth inhibition, with more robust T-cell infiltration at 40 mg/kg.
• Melanoma models (B16-F10, C57BL/6 mice): Single high dose of 800 μg/mouse i.p..
• Blood pressure studies (general mouse models): Low dose regimen of 150 μg i.p..
• General tumor studies: 1 mg/dose i.p., twice weekly for 4 weeks.

Notable considerations:

• Frequency: Varies by study but often ranges from two to three times weekly.
• Single vs. multiple dosing: Some models (e.g., metastatic melanoma) employ single high-dose injections, while others (solid tumors or long-term inhibition studies) use repeated doses.
• Dose selection rationale: Lower doses may reprogram immune cell phenotypes and alter the tumor microenvironment differently than high-dose regimens.
• Combination therapies: Regimens are sometimes adapted in combination with other antibodies (e.g., IMC-1C11) or immunotherapies to maximize efficacy.

In summary, DC101 dosing regimens are highly model-dependent, with variations in dose (from 150 μg to 40 mg/kg), schedule (single or repeated), and objectives (angiogenesis, immune modulation, etc.) according to the biology of the model and research goals.