VEGFR2-169

Summary

VEGFR2-169 is a synthetic peptide vaccine that targets the vascular endothelial growth factor receptor‑2 (VEGFR2), a protein over‑expressed on tumor‑associated blood vessels. Developed as an investigational cancer immunotherapy, it is administered by subcutaneous (or intramuscular) injection, often in combination with standard chemotherapy, to stimulate a cytotoxic T‑cell response against VEGFR2‑expressing endothelial cells and inhibit tumor angiogenesis, and may improve disease control in advanced pancreatic and gastric cancers.

Mechanism of Action

The peptide comprises an HLA‑A24‑restricted epitope derived from the intracellular domain of VEGFR2. After injection, antigen‑presenting cells process the peptide and present it on HLA‑A24 molecules, priming CD8⁺ cytotoxic T lymphocytes. These CTLs recognize VEGFR2‑expressing endothelial cells within the tumor vasculature, leading to targeted killing and disruption of angiogenic blood‑vessel formation that supports tumor growth. The approach aims to bypass direct tumor cell targeting and instead starve the tumor by eliminating its blood supply.

What the Research Shows

Early‑phase clinical studies have evaluated VEGFR2‑169 in patients with advanced pancreatic or gastric cancer. In a phase I trial of 18 pancreatic cancer patients receiving weekly subcutaneous injections of 0.5–2 mg VEGFR2‑169 together with gemcitabine, no dose‑limiting toxicities were observed. Specific CTL responses were detected in 11 patients (61 %) and the disease‑control rate was 67 %, with a median overall survival of 8.7 months. A subsequent phase I/II study in 22 HLA‑A24‑positive gastric cancer patients combined VEGFR2‑169 (and a VEGFR1 peptide) with S‑1 and cisplatin. CTL induction occurred in 18 patients (82 %) and the disease‑control rate after two cycles reached 100 %, with median overall survival of 14.2 months. Patients who mounted a VEGFR2‑169‑specific CTL response survived longer than non‑responders. Across studies, the vaccine was well tolerated, with only mild injection‑site inflammation reported.

Reported Benefits

VEGFR2‑169 consistently elicits VEGFR2‑specific cytotoxic T‑cell responses in a majority of treated patients, indicating strong immunogenicity even when given with chemotherapy. Early trials report disease‑control rates of 67 % in pancreatic cancer and 100 % after two cycles in gastric cancer, and median overall survivals of 8.7 and 14.2 months respectively, suggesting potential clinical benefit. The vaccine’s targeted anti‑angiogenic mechanism may complement standard chemotherapy and offers a strategy to impair tumor blood‑vessel formation.

Limitations of the Evidence

Evidence for VEGFR2‑169 is limited to small, non‑randomised phase I and phase I/II studies involving fewer than 30 patients per trial. The reported outcomes lack control arms, making it impossible to separate vaccine effects from chemotherapy. Immunogenicity appears restricted to HLA‑A24‑positive individuals, limiting broader applicability. Long‑term survival benefits, optimal dosing, and efficacy across tumor types remain undefined, and no regulatory approval has been granted.

Safety Considerations

Across the reported trials, VEGFR2‑169 was well tolerated. No grade 4 or higher adverse events or dose‑limiting toxicities were observed. The most common adverse effect was a mild to moderate inflammatory reaction at the injection site, reported in the majority of patients. Systemic toxicities were absent, and laboratory parameters remained stable. These findings suggest a favorable safety profile when the peptide is administered subcutaneously alongside standard chemotherapeutic regimens.

How It Is Administered

VEGFR2‑169 is formulated as a peptide vaccine and administered by subcutaneous (or intramuscular) injection, typically once weekly. Early studies used a dose‑escalation scheme of 0.5 mg, 1 mg and 2 mg per body, often in combination with gemcitabine for pancreatic cancer or S‑1 plus cisplatin for gastric cancer. The vaccine is supplied as a sterile solution for injection.

Routes of Administration

Goals & Uses

• Anti‑angiogenesisVascularModerate
• Cancer immunotherapyOncologyModerate

Contraindications

• Autoimmune diseaseImmuneModerateMay worsen or interact with immune-mediated disease
• Immunosuppressive therapyPharmacologicalModerate

Adverse Effects

• Injection‑site erythemaLocalCommon
• Fever / flu‑like symptomsSystemicUncommon

Drug Interactions

• TNF‑α inhibitorsModerate
• CorticosteroidsModerate

Population Constraints

• Pregnant womenReproductiveAbsolute
• Children < 12 yAgeRelative

Regulatory Status

• European UnionInvestigationalNo marketing authorization
• United StatesInvestigationalPhase I/II oncology trials only
• United KingdomInvestigationalClinical trial use only

Evidence & Sources

• [The development of a novel cancer vaccine using Peptide vaccine for patients with advanced pancreatic cancer]
  Journal ArticleLowMiyazawa M, Yamaue H2011-01-01T00:00:00.000000Z
• Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer
  Journal ArticleModerateMiyazawa M, et al.2010-01-01T00:00:00.000000Z
• Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer
  Journal ArticleModerateMasuzawa T, et al.2012-01-01T00:00:00.000000Z

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