Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma

Cutmore, Lauren; Brown, Nicholas F.; Raj, Deepak; Chauduri, S.; Wang, P.; Maher, John; Wang, Y.; Lemoine, Nick R.; Marshall, John F.

doi:10.1016/j.pan.2020.02.006

Cited by 11 publications

(9 citation statements)

References 247 publications

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“…When T cells encounter specific tumor antigens, the single chain variable fragments (scFv) in the antigen recognition region will bind to tumor antigens and then directly activate T cells and stimulate the secretion of cytokines, which can attack and kill tumor cells. Chimeric antigen receptor-modified T cell (CAR-T) therapy is based on this mechanism and has been achieved good results [ 19 ]. T cells are the key effectors of the tumor immune response.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Prognostic and Immune-Related Genes in Pancreatic Cancer

Yang

et al. 2021

Computational and Mathematical Methods in Medicine

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Pancreatic cancer (PC) is a malignant tumor with poor prognosis. The poor effect of surgery and chemotherapy makes the research of immunotherapy target molecules significant. Therefore, identifying the new molecular targets of PC is important for patients. In our study, we systematically analyzed molecular correlates of pancreatic cancer by bioinformatic analysis. We characterized differentially expressed analysis based on the TCGA pancreatic cancer dataset. Then, univariate Cox regression was employed to screen out overall survival- (OS-) related DEGs. Based on these genes, we established a risk signature by the multivariate Cox regression model. The ICGC cohort and GSE62452 cohort were used to validate the reliability of the risk signature. The impact of T lymphocyte-related genes from risk signature was confirmed in PC. Here, we observed the correlation between the T lymphocyte-related genes and the expression level of targeted therapy. We established a five-mRNA (LY6D, ANLN, ZNF488, MYEOV, and SCN11A) prognostic risk signature. Next, we identified ANLN and MYEOV that were associated with T lymphocyte infiltrations ( P < 0.05 ). High ANLN and MYEOV expression levels had a poorer prognosis in decreased T lymphocyte subgroup in PC. Correlation analysis between ANLN and MYEOV and immunomodulators showed that ANLN and MYEOV may have potential value in pancreatic cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Prognostic and Immune-Related Genes in Pancreatic Cancer

Yang

et al. 2021

Computational and Mathematical Methods in Medicine

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“…However, solid tumors are often very poorly-perfused and have a dense, fibrotic and highly immunosuppressive microenvironment, which makes the application of CAR-Ts technically challenging. Advances on CAR-T in PDAC treatment were review in recent articles [148][149][150].…”

Section: T Cells In Focusmentioning

confidence: 99%

Pancreatic Cancer and Its Microenvironment—Recent Advances and Current Controversies

Stopa

Kusiak

Szopa

et al. 2020

IJMS

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Pancreatic ductal adenocarcinoma (PDAC) causes annually well over 400,000 deaths world-wide and remains one of the major unresolved health problems. This exocrine pancreatic cancer originates from the mutated epithelial cells: acinar and ductal cells. However, the epithelia-derived cancer component forms only a relatively small fraction of the tumor mass. The majority of the tumor consists of acellular fibrous stroma and diverse populations of the non-neoplastic cancer-associated cells. Importantly, the tumor microenvironment is maintained by dynamic cell-cell and cell-matrix interactions. In this article, we aim to review the most common drivers of PDAC. Then we summarize the current knowledge on PDAC microenvironment, particularly in relation to pancreatic cancer therapy. The focus is placed on the acellular stroma as well as cell populations that inhabit the matrix. We also describe the altered metabolism of PDAC and characterize cellular signaling in this cancer.

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“…Unfortunately, the successes of CAR T cells is yet to be widely clinically applicable. This is due to many factors including lack of appropriate tumour specific antigens, the immunosuppressive nature of the tumour microenvironment, variability in product quality and high costs (previously discussed by Cutmore et al [137]. Use of allogeneic CAR expressing cells could overcome some of these obstacles.…”

Section: Discussionmentioning

confidence: 99%

Current Perspectives on the Use of off the Shelf CAR-T/NK Cells for the Treatment of Cancer

Cutmore

Marshall

2021

Cancers

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CAR T cells have revolutionised the treatment of haematological malignancies. Despite this, several obstacles still prohibit their widespread use and efficacy. One of these barriers is the use of autologous T cells as the carrier of the CAR. The individual production of CAR T cells results in large variation in the product, greater wait times for treatment and higher costs. To overcome this several novel approaches have emerged that utilise allogeneic cells, so called “off the shelf” CAR T cells. In this Review, we describe the different approaches that have been used to produce allogeneic CAR T to date, as well as their current pre-clinical and clinical progress.

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Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma

Cited by 11 publications

References 247 publications

Bioinformatic Analysis of Prognostic and Immune-Related Genes in Pancreatic Cancer

Bioinformatic Analysis of Prognostic and Immune-Related Genes in Pancreatic Cancer

Pancreatic Cancer and Its Microenvironment—Recent Advances and Current Controversies

Current Perspectives on the Use of off the Shelf CAR-T/NK Cells for the Treatment of Cancer

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