A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) Targeting Patient-unique Tumor-specific Neoantigens, With in Vivo CD40 Activation and PD-1 Blockade, for Patients With Incurable Cancers

This is a phase I/Ib study of adoptively transferred T-cell receptor gene-engineered T cells (TCR-T) targeting tumor-specific antigens, with in vivo CD40 activation and PD-1 blockade, for patients with incurable cancers. The study design is a safety lead-in TCR-T with CD40/PD-1 (3+3), followed by Simon's Two-Stage expansion design, 80% power and 5% one-sided alpha: stage-one futility assessment at n = 10; stage-two assessment at n = 22, (accrual up to 24 to allow for potential study drop-out).

开始日期2023-04-03

申办/合作机构

Providence Health & Services

[+1]

NCT04520711 / Active, not recruiting临床1期IIT

Hotspot TCR-T: A Phase I/Ib Study of Adoptively Transferred T-cell Receptor Gene-engineered T Cells (TCR-T) Targeting Tumor-Specific Neoantigens, With in Vivo CD40 Activation and PD-1 Blockade, for Patients With Incurable Cancers (2020000584)

开始日期2022-02-08

申办/合作机构

Providence Health & Services

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项与 TCR-transduced T cells(Providence Health & Services) 相关的文献（医药）

2017-01-01·Journal of Cancer3区 · 医学

The Multi-Purpose Tool of Tumor Immunotherapy: Gene-Engineered T Cells

3区 · 医学

ReviewOA

作者: Du, Peixin ; Wang, Guoping ; Wang, Yongsheng ; Mo, Zeming

A detailed summary of the published clinical trials of chimeric antigen receptor T cells (CAR-T) and TCR-transduced T cells (TCR-T) was constructed to understand the development trend of adoptive T cell therapy (ACT). In contrast to TCR-T, the number of CAR-T clinical trials has increased dramatically in China in the last three years. The ACT seems to be very prosperous. But, the multidimensional interaction of tumor, tumor associated antigen (TAA) and normal tissue exacerbates the uncontrolled outcome of T cells gene therapy. It reminds us the importance that optimizing treatment security to prevent the fatal serious adverse events. How to balance the safety and effectiveness of the ACT? At least six measures can potentially optimize the safety of ACT. At the same time, with the application of gene editing techniques, more endogenous receptors are disrupted while more exogenous receptors are expressed on T cells. As a multi-purpose tool of tumor immunotherapy, gene-engineered T cells (GE-T) have been given different functional weapons. A network which is likely to link radiation therapy, tumor vaccines, CAR-T and TCR-T is being built. Moreover, more and more evidences indicated that the combination of the ACT and other therapies would further enhance the anti-tumor capacity of the GE-T.

2011-03-01·Journal of Clinical Oncology1区 · 医学

Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1

1区 · 医学

Article

作者: Mackall, Crystal L. ; Nahvi, Azam V. ; Lee, Chyi-Chia Richard ; Li, Yong F. ; El-Gamil, Mona ; Yang, James C. ; Robbins, Paul F. ; Restifo, Nicholas P. ; Rosenberg, Steven A. ; Hughes, Marybeth S. ; Dudley, Mark E. ; Morgan, Richard A. ; Levy, Catherine L. ; Feldman, Steven A. ; Laurencot, Carolyn ; Helman, Lee J. ; Schwarz, Susan L. ; Sherry, Richard M. ; Wunderlich, John R. ; Raffeld, Mark ; Kammula, Udai S.

Purpose Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma. Patients and Methods A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1–positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Results Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma. Conclusion These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.

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疲劳	临床1期	美国	Providence Health & Services	2022-02-08
发热	临床1期	美国	Providence Health & Services	2022-02-08
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