TCR-T Cell Immunotherapy of Lung Cancer and Other Solid Tumors

Официальное название

TCR-T Cells Targeting Cancer Cells for Immunotherapy of Lung Cancer and Other Solid Tumors: Phase I Clinical Trial

Обзор

Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh tissure of lung cancer and other solid tumors. Coculture will be utilized to screen tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in vivo studies, a large number of TCR-T cells will be introduced back into the patients via vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study, the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will firstly be assessed.

Подробное описание

1. Choose appropriate patients with KK-LC-1 expression in advanced lung cancer or other solid tumors and matched MHC-A11 typing, with written consent for this study; For cancer without expression of KK-LC-1, fresh tumor tissue should be obtained for RNA/DNA sequencing to computationally identify neoantigen peptides that can be captured by specifically personizedly synthesized poly-MHCI which can be further used to fish appropriate T cells from the patient. 2. Perform biopsy to obtain tissue from tumor/lymph node for organoids, TILs, DC and T cells culture, coculture to screening anti-tumor T cells, establish and select monoclonal T cells for TCR cloning; 3. Clone TCR sequence that targets KK-LC-1 or neoantigens; collect PBMCs from the blood of the patients, isolate and activate the T cells and generate the TCR-T cells; 4. Test the quality and killing activity of the TCR-T cells in vitro and then transplant back the patients via systemic (vein and/or artery) or local injections, and follow up closely to collect related clinical data as needed; 5. Evaluate the clinical results as needed.

Вмешательства

• Биопрепарат TCR-T cells
  Engineering TCR-T cells targeting lung tumor and other solid tumor will be transfused back the patients.

Первичные конечные точки

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

Вторичные конечные точки (1)

• Percent of Patients with best response as either complete remission or partial remission [Срок оценки: three months]

Критерии участия

Критерии включения

• patients with advanced lung tumor or other solid tumor where biopsy is obtainable
• Life expectancy >12 weeks
• Child-Pugh-Turcotte score <7
• Adequate heart,lung,liver,kidney function
• Available autologous transduced T cells with greater than or equal to 20% expression of targeted TCR sequences determined by flow-cytometry and killing of tumor cells greater than or equal to 20% in cytotoxicity assay
• Informed consent explained to, understood by and signed by patient/ guardian. Patient/guardian given copy of informed consent. -

Критерии исключения

• Had accepted gene therapy before;
• Tumor size more than 25cm;
• Severe virus infection such as HBV, HCV, HIV, et al
• Known HIV positivity
• History of lung transplantation
• 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 — Guanzhou

Идентификаторы

NCT: NCT03778814 · ZZTCRT-006

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗