臨床研究等提出・公開システム

WT1 peptide-pulsed dendritic cell therapy for wet age-related macular degeneration

WT1 peptide-pulsed dendritic cell therapy for wet age-related macular degeneration

Yoshida Hiroshi

Mar. 27, 2024

2

Case 1 Age: 73 years; Sex: Female; Affected eye: Left; Diagnosis: Type 1 MNV (PCV subtype); Baseline decimal visual acuity: 0.6; Baseline OCT findings: Subretinal fluid; Other ocular comorbidities: Cataract. Case 2 Age: 80 years; Sex: Female; Affected eye: Right; Diagnosis: Type 1 MNV; Baseline decimal visual acuity: 0.7; Baseline OCT findings: Macular hemorrhage; Other ocular comorbidities: None.

May 7, 2021: Study initiation (date of public disclosure on jRCT) November 25, 2021: Start of enrollment (date of first patient registration) December 19, 2022: Completion of enrollment (date of second patient registration) March 27, 2024: End of study period for all participants September 30, 2025: Database lock Informed consent obtained: 2 cases WT1 dendritic cell administration: 2 cases

Both patients experienced mild injection-site reactions associated with subcutaneous administration of the WT1 peptide-pulsed dendritic cell vaccine; however, no adverse events attributable to the regenerative medical intervention occurred, and all 15 planned vaccine doses were completed. In addition, no adverse events related to intravitreal aflibercept injections were observed in either patient.

During administration of the WT1 peptide-pulsed dendritic cell vaccine, WT1-specific IFN-gamma and TNF-alpha production by CD4- and CD8-positive T cells was observed in both cases, indicating transient induction of an immune response. However, cytokine levels returned to baseline within one month after completion of vaccination, and sustained long-term immunity was not achieved. Clinical outcomes differed between the two cases: one experienced disease recurrence, whereas the other maintained remission. Factors such as disease subtype, dosing interval, sensitivity to treatment, host immune competence, and intralesional WT1 expression levels may have contributed to these differences. Neither delayed-type hypersensitivity (DTH) responses nor WT1-specific CD8-positive T cells were detected, suggesting that induction and detection of WT1-specific immunity may be more difficult in age-related macular degeneration than in cancer.

These findings suggest that continuous administration of the WT1 peptide-pulsed dendritic cell vaccine at two-week intervals may contribute to the control of disease activity and could represent a complementary strategy to existing therapies in patients with age-related macular degeneration.

June. 01, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCTc030210068

Gunji Hisato

The Jikei University Kashiwa Hospital

163-1 Kashiwashita,Kasiwa-shi,Chiba-ken

hg6727@jikei.ac.jp

Nakamura Masaki

The Jikei University Katsushika Medical Center

6-41-2 Aoto,Katsushika-ku,Tokyo

+81-3-3633-2111

h20ms.loveinthisclub@gmail.com

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Clinically diagnosed with wet age-related macular degeneration
2) The name of the disease in 1) has been announced.
3) HLA type is HLA-A (A * 2402, A * 0201, A * 0206), HLA-DR (DRB1 * 0101, DRB1 * 0405, DRB1 * 0802, DRB1 * 0803, DRB1 * 0901, DRB1 * 1201, DRB1 * 1403, DRB1 * 1501, DRB1 * 1502, DRB5 * 0102), HLA-DP (DPB1 * 0201, DPB1 * 0202, DPB1 * 0402, DPB1 * 0501, DPB1 * 0901), HLA-DQ (DQB1 * 0301, One of DQB1 * 0302, DQB1 * 0401, DQB1 * 0501, DQB1 * 0601, DQB1 * 0602.
4) Outpatient visits are possible according to the research implementation schedule.
5) Patient without treatment for cancer.
6) Over 50 years of age
7) Patients who retain the functions of major organs (confirmed by pre-registration examination).
8) Written consent from the patient has been obtained for participation in this study.
9) Meet the apheresis eligibility criteria for dendritic cell production

1) Have an uncontrolled infectious disease
2) Serious complications: malignant hypertension, severe congestive heart failure, severe coronary failure, unstable edema or myocardial infarction within 12 months, severe arrhythmia requiring medication and more than 2nd degree Patients with conduction abnormalities such as AV block, liver cirrhosis, uncontrolled diabetes, pulmonary fibrosis, interstitial pneumonia, marked peripheral edema, etc. active infections, active hepatitis B
3) Patients who are considered unsuitable for participation in this clinical trial due to complications or whose safety may be compromised due to serious medical events.
4) Cases in which antitumor treatment such as chemotherapy / radiochemotherapy was performed within 1 year
5) Have serious complications
6) Patients with myelodysplastic syndrome, myelodysplastic / myeloproliferative disorders and chronic myelogenous leukemia
7) History of severe drug hypersensitivity (excluding iodine contrast media)
8) Patients with severe mental illness
9) Patients with autoimmune disease
10) Patients with a history of allergies to OK-432 and penicillin G
11) Pregnant or lactating women
12) Pregnant women who are not willing to contracept

Both

wet age-related macular degeneration

<WT1 peptide pulsed dendritic cell vaccine>
Approximately 10,000,000 WT1 peptide pulsed dendritic cell vaccines are injected intradermally or subcutaneously at a total of 4 sites on either the extensor surfaces of both upper arms~axillae or the anterior surfaces of both thighs. The vaccine may be continued once every 2 weeks unless skip criteria are met. However, the maximum number of doses is 15.

<Aflibercept>
(1) Dosing Criteria
Aflibercept (genetical recombination) 2 mg (0.05 mL) should be administered intravenously once every month for 3 consecutive induction cycles.
(2) Additional dosage standard
During the treatment period of WT1 peptide-pulsed dendritic cell vaccine, aflibercept intravitreal administration should be started as a fixed dose every 3 months after the 3rd dose (16 weeks after starting treatment), 7th dose (24 weeks after starting treatment), 11th dose (32 weeks after starting treatment), and post-observation period if the following findings are observed.

Translated with www.DeepL.com/Translator (free version)
1)Central retinal thickness (CRT) increases by 100 micrometes or more from the minimum value
2)New CNV appears
3)New macular hemorrhage appears

Safety(Adverse event rate,Rate of serious adverse events)

(1) Average change in best-corrected visual acuity from post-treatment (baseline)
(2) Amount of change in central retinal thickness
(3) Amount of change in lesion area of choroidal neovascularization
(4) Delayed hypersensitivity reaction to WT1 peptide
(5) WT1-specific immunological monitoring
(6) WT1 non-specific immune response

Complete

+81-3-3433-1111

Dec. 09, 2022