Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer.
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2019-12
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Adoptive T cell immunotherapy with cytokine-induced killer cells (CIKs) has been demonstrated to prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate whether the expansion of effector T cells and the decrease of regulatory T cells (Tregs) that occurred during the ex vivo generation of DC-CIKs were associated with improved clinical outcome in patients who received treatment. CIKs were generated ex vivo over a 28-day period from the peripheral blood apheresis product of 163 patients with advanced cancer (including 30 with NSCLC). CIKs were also generated from an additional cohort of 65 patients with NSCLC over a 15-day period. The progression-free survival (PFS) and overall survival (OS) time of patients treated with CIKs was determined by reviewing the patients' medical records. The number of CIKs gradually increased during the culture period and peaked at day 15, followed by a slight decline until day 28. Similarly, the percentages of T cell subtypes associated with anti-tumor activity (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+) peaked at day 15. Although the percentage of CD4+CD25+CD127+ Tregs increased by day 7, a decrease was subsequently observed. Among the 95 patients with NSCLC, those with a post/pre-culture ratio of CD8+CD28+ T lymphocytes >2.2 had significantly better PFS and OS compared with those with ratios ≤2.2. Those with a post/pre-culture CD4+CD25+CD127+ Treg ratio ≤0.6 had significantly better OS and PFS compared with those with ratios >0.6. The peak expansion of CIKs from peripheral blood mononuclear cells occurred at day 15 of ex vivo culture. PFS and OS were associated with post/pre-culture CD8+CD28+ T lymphocyte ratio >2.2 and post/pre-culture CD4+CD25+CD127+ Treg ratio <0.6 in the CIKs of patients with advanced NSCLC treated with adoptive T cell immunotherapy. Further efforts are underway to optimize the DC-CIK infusion for cancer immunotherapy.
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Huang, Lefu, Guoliang Qiao, Michael A Morse, Xiaoli Wang, Xinna Zhou, Jiangping Wu, Amy Hobeika, Jun Ren, et al. (2019). Predictive significance of T cell subset changes during ex vivo generation of adoptive cellular therapy products for the treatment of advanced non-small cell lung cancer. Oncology letters, 18(6). pp. 5717–5724. 10.3892/ol.2019.10964 Retrieved from https://hdl.handle.net/10161/19748.
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Scholars@Duke
Michael Aaron Morse
We are studying the use of immune therapies to treat various cancers, including gastrointestinal, breast, and lung cancers and melanoma. These therapies include vaccines based on dendritic cells developed in our laboratory as well as vaccines based on peptides, viral vectors, and DNA plasmids. Our group is also a national leader in the development and use of laboratory assays for demonstrating immunologic responses to cancer vaccines. Finally, we are developing immunotherapies based on adoptive transfer of tumor and viral antigen-specific T cells.
Our current clinical trials include phase I and II studies of immunotherapy for: patients with metastatic malignancies expressing CEA, pancreatic cancer, colorectal cancer, breast cancer, and ovarian cancer, and leukemias following HSCT. My clinical area of expertise is in gastrointestinal oncology, in particular, the treatment of hepatic malignancies, and malignant melanoma.
Key words: dendritic cells, immunotherapy, vaccines, T cells, gastrointestinal oncology, melanoma, hepatoma
Amy Claudine Hobeika
Jun Ren
Jun Ren MD, PhD joined Duke University as faculty from 2008. He has actively worked with Professor Kim Lyerly to create the global cancer programs featured on education and research on cancer immunotherapy and cancer vaccines program. They have been keeping pursuing to set up the win-to-win platform thought overcoming these differences and difficulties between US and China since 2008. He and Kim Lyerly secured the transitional research for cancer immunotherapy and achieved clinical research success and expand the global academic prospectives of Duke University.
Herbert Kim Lyerly
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