Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

开始日期2021-01-01

申办/合作机构

广州医科大学附属第二医院

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100 项与 EGFR-CAR-TILs(Guangdong Zhaotai InVivo Biomedicine) 相关的临床结果

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100 项与 EGFR-CAR-TILs(Guangdong Zhaotai InVivo Biomedicine) 相关的转化医学

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100 项与 EGFR-CAR-TILs(Guangdong Zhaotai InVivo Biomedicine) 相关的专利（医药）

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项与 EGFR-CAR-TILs(Guangdong Zhaotai InVivo Biomedicine) 相关的文献（医药）

2021-01-01·Therapeutic Advances in Vaccines and Immunotherapy

Generating CAR T cells from tumor-infiltrating lymphocytes

Article

作者: Giuffrida, Lauren ; Henderson, Melissa A. ; Kershaw, Michael H. ; Darcy, Phillip K. ; Mills, Jane K. ; Westwood, Jennifer A. ; Gyorki, David E. ; Neeson, Paul J. ; Petrone, Pasquale

Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.

PLOS ONE

Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function

Article

作者: Fisher, Jonathan ; Anderson, John ; Flutter, Barry ; Barone, Giuseppe ; Ollé Hurtado, Marina ; Stafford, Sian ; Jain, Neha ; Wolbert, Jolien ; Barton, Jack ; Majani, Yvonne

Adoptive transfer of ex vivo expanded tumor infiltrating lymphocytes (TILs) has led to clinical benefit in some patients with melanoma but has not demonstrated convincing efficacy in other solid cancers. Whilst the presence of TILs in many types of cancer is often associated with better clinical prognosis, their function has not been systematically evaluated across cancer types. Responses to immunological checkpoint inhibitors in a wide range of cancers, including those for which adoptive transfer of expanded TILs has not shown clinical benefit, has clearly delineated a number of tumor type associated with tumor-reactive lymphocytes capable of effecting tumor remissions. Neuroblastoma is an aggressive childhood solid cancer in which immunotherapy with GD2-directed antibodies confers a proven survival advantage through incompletely understood mechanisms. We therefore evaluated the feasibility of ex vivo expansion of TILs from freshly resected neuroblastoma tumors and the potential therapeutic utility of TIL expansions. TILs were successfully expanded from both tumor biopsies or resections. Significant numbers of NKT and γδT cells were identified alongside the mixed population of cytotoxic (CD8+) and helper (CD4+) T cells of both effector and central memory phenotypes. Isolated TILs were broadly non-reactive against autologous tumor and neuroblastoma cell lines, so enhancement of neuroblastoma killing was attained by transducing TILs with a second-generation chimeric antigen receptor (CAR) targeting GD2. CAR-TILs demonstrated antigen-specific cytotoxicity against tumor cell lines. This study is the first to show reproducible expansion of TILs from pediatric neuroblastoma, the high proportion of innate-like lymphocytes, and the feasibility to use CAR-TILs therapeutically.

Cancers

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

Article

作者: Rönnberg, Henrik ; Saellström, Sara ; Nilsson, Lisa M. ; Olofsson Bagge, Roger ; Bucher, Valentina ; Alsén, Samuel ; Forsberg, Elin M. V. ; Riise, Rebecca ; Nilsson, Jonas A. ; Ny, Lars ; Karlsson, Joakim ; Hemminki, Akseli E.

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.

100 项与 EGFR-CAR-TILs(Guangdong Zhaotai InVivo Biomedicine) 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01
脑癌	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01
乳腺癌	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01
结直肠癌	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01
肝癌	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01
肺癌	临床1期	中国	广东昭泰体内生物医药科技有限公司	2021-01-01