Mesothelin/GPC3/GUCY2C-CAR-T Cells Against Cancers

Официальное название

Mesothelin/GPC3/GUCY2C Targeted CAR-T for Immunotherapy of Pancreatic Cancer: Phase I Clinical Trial

Обзор

The second generation of mesothelin targeted CAR-T cells that secret a fusion protein of IL21 and scfv against PD1 have been constructed and their anti-cancer function has been verified by multiple in vitro and in vivo studies. Clinical studies will be performed to test anti-cancer function of the CAR-T cells for immunotherapy of human cancer patients with Mesothelin expressions. In this phase I study, the safety, tolerance, and preliminary efficacy of the Mesothelin-CAR-T cell immunotherapy on human cancers will firstly be evaluated.

Подробное описание

1. Choose appropriate patients with advanced pancreatic cancer or other cancers, with written consent for this study; 2. Perform biopsy to determine the expression of Mesothelin of the tumors by western blotting or IHC; 3. Collect blood from the patients and isolate mononuclear cells, activate the T cells and transfect the T cells with Mesothelin targeting CAR, amplify the transfected T cells as needed, test the quality and killing activity of the CAR-T cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as required; 4. To enhance the killing capability, cotreatment the patients with PD1/PDL1/CTLA4 antibodies may be applied; 5. Evaluate the clinical results as needed.

Вмешательства

• Биопрепарат CAR-T cells
  Transfer CAR-T cells into patients for anti-ancer therapy.

Первичные конечные точки

• Number of Patients with Dose Limiting Toxicity [Срок оценки: six months]

Вторичные конечные точки (2)

• Percent of Patients with best response as either complete remission or partial remission. [Срок оценки: six months]
• Median CAR-T cell persistence [Срок оценки: Six years]

Критерии участия

Критерии включения

1\. Patients with advanced cancer that expresses Mesothelin protein; 2. Life expectancy >12 weeks; 3. Adequate heart, lung, liver, kidney, and blood function; 4. Available autologous transduced T cells with greater than or equal to 20% expression of Mesothelin-CAR determined by flow-cytometry and killing of Mesothelin-positive targets greater than or equal to 20% in cytotoxicity assay; 5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.

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Критерии исключения

• Had accepted gene therapy before;
• Severe virus infection such as HBV, HCV, HIV, et al;
• Known HIV positivity;
• Active infectious disease related to bacteria, virus,fungi,et al;
• Other severe diseases that the investigators consider not appropriate;
• Pregnant or lactating women;
• Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);
• Other conditions that the investigators consider not appropriate. -

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Second Affiliated Hospital of Guangzhou Medical University — Гуанчжоу

Идентификаторы

NCT: NCT05779917 · ZZFC004CAR-018

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗