Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells

You, Fengming; Jiang, Licui; Zhang, Bozhen; Lü, Qiang; Zhou, Qiao; Liao, Xiaoyang; Wu, Hong; Du, Ke; Zhu, You‐cai; Meng, Hua; Gong, Zhishu; Zong, Yunhui; Huang, Lei; Lu, Man; Tang, Jirong; Li, Yafen; Zhai, Xiaochen; Wang, Xiangling; Ye, Sisi; Chen, Dan; Yuan, Lei; Lin, Qian; Yang, Lin

doi:10.1007/s11427-016-5024-7

Cited by 126 publications

(91 citation statements)

References 55 publications

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“…A pooled prevalence of 37.2% [95% CI, 28.6%-46.8%; I 2 72.6%] was demonstrated among patients treated with CAR-T cell therapy. In post hoc subgroup analyses, the prevalence of neurotoxicity did not differ between cancer types, costimulatory domains, or trial phase (Appendices 13-15).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

133

122

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Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception -November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy. (M.M. Lalu). @manojlalu (M.M. Lalu).

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Section: Resultsmentioning

confidence: 99%

“…A pooled prevalence of 13.6% [95% CI, 0.7%-79.0%; I 2 72.8%] was demonstrated among patients treated with CAR-T cell therapy.…”

Section: Resultsmentioning

confidence: 99%

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Grigor

Fergusson

Kekre

et al. 2019

Transfusion Medicine Reviews

133

122

View full text Add to dashboard Cite

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“…At present, a phase I clinical trial of anti-CD133 CAR-T cells in patients with relapsed and/or chemotherapy refractory advanced malignancies is ongoing (NCT02541370). In addition to above antigens, fibroblast activation protein (FAP) [139, 140], NY-ESO-1 [141], MUC1 [142], foliate receptor [143, 144], and IL13Rα2 [145, 146] are also potential target antigens for immunotherapy.…”

Section: Target Antigen Expressing On Solid Tumor Cell Surfacementioning

confidence: 99%

Chimeric antigen receptor T cells: a novel therapy for solid tumors

et al. 2017

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The chimeric antigen receptor T (CAR-T) cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs) expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy.

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“…: NM_001127593) extracellular domain (ECD), the CD8a extracellular domain (NM_001768), the CD28 transmembrane domain (TM), and tandem CD28 [26] and 4-1BB [27] co-activation domains linked to the CD3ζ signaling domain previously made in our laboratory [28]. CD64-BB-ζ's modular design is similar to that of CD16-BB-ζ, except for the CD64 cDNA (AK291451) being replaced with the CD16 cDNA (Figure 1A) sequence.…”

Section: Resultsmentioning

confidence: 99%

“…The FcRγIIIa CD16 (158F) cDNA extracellular domain (NM_001127593), FcγRI (CD64) cDNA extracellular domain (AK291451), and the CD8a (NM_001768) extracellular domain were obtained from Origene and synthesized. Signal peptide (SP), CD28 transmembrane domain, two co-stimulatory domains (CD28 and 4-1BB) that define the construct as a “third generation” CAR, and a CD3ζ intracellular signaling domain (ICP) were sub-cloned from a MUC1-specific CAR previously made in our laboratory [28]. These molecules were assembled in various combinations using splicing by overlapping extension by PCR (SOE-PCR).…”

Section: Methodsmentioning

confidence: 99%

Gene-modified NK-92MI cells expressing a chimeric CD16-BB-ζ or CD64-BB-ζ receptor exhibit enhanced cancer-killing ability in combination with therapeutic antibody

et al. 2017

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Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins. The construct includes the low-affinity Fc receptor CD16 (158F) or the high-affinity Fc receptor CD64, with the addition of the CD8a extracellular domain, CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the signaling domain from CD3ζ. The resulting chimeric receptors, termed CD16-BB-ζ and CD64-BB-ζ, were used to generate modified NK-92MI cells expressing the chimeric receptor, which were named NK-92MIhCD16 and NK-92MIhCD64 cells, respectively. We found that NK-92MIhCD16 and NK-92MIhCD64 cells significantly improved cytotoxicity against CD20-positive non-Hodgkin's lymphoma cells in the presence of rituximab. These results suggest that the chimeric receptor-expressing NK-92MI cells may enhance the clinical responses to currently available anticancer monoclonal antibodies.

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Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells

Cited by 126 publications

References 55 publications

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

Chimeric antigen receptor T cells: a novel therapy for solid tumors

Gene-modified NK-92MI cells expressing a chimeric CD16-BB-ζ or CD64-BB-ζ receptor exhibit enhanced cancer-killing ability in combination with therapeutic antibody

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