Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target

Khan, Maliha; Carmona, Selena; Sukhumalchandra, Pariya; Roszik, Jason; Philips, Anne V.; Perakis, Alexander A.; Kerros, Celine; Zhang, Mao; Qiao, Na; John, Lisa S. St.; Zope, Madhushree; Goldberg, Jonathan; Qazilbash, M.; Jakher, Haroon; Clise-Dwyer, Karen; Qiu, Yihua; Mittendorf, Elizabeth A.; Molldrem, Jeffrey J.; Kornblau, Steven M.; Alatrash, Gheath

doi:10.3389/fimmu.2017.01975

Cited by 21 publications

(13 citation statements)

References 52 publications

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“…To evaluate the capacity of different cell lines to be used as model APCs for presentation of WT1-derived epitopes by HLA-A2, the expression of surface HLA-A2 and natural intracellular WT1 proteins of four potential cell lines was quantified: T2 [24], U266 [25], K562-A2 [26] and Raji-A2 [27] cells ( Figure 1). All cell lines expressed HLA-A2, with percentages ranging from 95% to 99% of HLA-A2-positive cells (Figure 1, upper panel).…”

Section: Quantitation Of Wt1-presenting Potential Odel Apcmentioning

confidence: 99%

Rapid Assessment of Functional Avidity of Tumor-Specific T Cell Receptors Using an Antigen-Presenting Tumor Cell Line Electroporated with Full-Length Tumor Antigen mRNA

Campillo-Davò

Versteven

Roex

et al. 2020

Cancers

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The functional avidity of T-cell receptor (TCR)-engineered T cells towards their cognate epitope plays a crucial role in successfully targeting and killing tumor cells expressing the tumor-associated antigen (TAA). When evaluating in vitro functional T-cell avidity, an important aspect that is often neglected is the antigen-presenting cell (APC) used in the assay. Cell-based models for antigen-presentation, such as tumor cell lines, represent a valid alternative to autologous APCs due to their availability, off-the-shelf capabilities, and the broad range of possibilities for modification via DNA or messenger RNA (mRNA) transfection. To find a valuable model APC for in vitro validation of TAA Wilms’ tumor 1 (WT1)-specific TCRs, we tested four different WT1 peptide-pulsed HLA-A2+ tumor cell lines commonly used in T-cell stimulation assays. We found the multiple myeloma cell line U266 to be a suitable model APC to evaluate differences in mean functional avidity (EC50) values of transgenic TCRs following transfection in 2D3 Jurkat T cells. Next, to assess the dose-dependent antigen-specific responsiveness of WT1 TCR-engineered 2D3 T cells to endogenously processed epitopes, we electroporated U266 cells with different amounts of full-length antigen WT1 mRNA. Finally, we analyzed the functional avidity of WT1 TCR-transfected primary CD8 T cells towards WT1 mRNA-electroporated U266 cells. In this study, we demonstrate that both the APC and the antigen loading method (peptide pulsing versus full-length mRNA transfection) to analyze T-cell functional avidity have a significant impact on the EC50 values of a given TCR. For rapid assessment of the functional avidity of a cloned TCR towards its endogenously processed MHC I-restricted epitope, we showcase that the TAA mRNA-transfected U266 cell line is a suitable and versatile model APC.

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Section: Quantitation Of Wt1-presenting Potential Odel Apcmentioning

confidence: 99%

Rapid Assessment of Functional Avidity of Tumor-Specific T Cell Receptors Using an Antigen-Presenting Tumor Cell Line Electroporated with Full-Length Tumor Antigen mRNA

Campillo-Davò

Versteven

Roex

et al. 2020

Cancers

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“…Recently, assays have incorporated cathepsins B, D, G, K, L, V and S quantification using IHC (from BC patients [73]), RT-PCR, Western analysis, reverse-phase protein arrays (from acute lymphoid leukemia patients, ALL [74]), cathepsin expression levels and activity analysis (from acute myeloid leukemia patients, AML [75]), in silico analysis and histological staining (from papillary thyroid cancer patients [76] and esophageal cancer patients [51]). All of these approaches look very encouraging and have offered high levels of accuracy and which highlight the therapeutic-targeting potential of cathepsins and their use as reliable prognostic markers [77,78].…”

Section: Cystatins and Cathepsins As Prognostic Markers In Cancermentioning

confidence: 99%

Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer

et al. 2019

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In keeping with recent developments in basic research; the importance of the Cathepsins as targets in cancer therapy have taken on increasing importance and given rise to a number of key areas of interest in the clinical setting. In keeping with driving basic research in this area in a translational direction; recent findings have given rise to a number of exciting developments in the areas of cancer diagnosis; prognosis and therapeutic development. As a fast-moving area of research; the focus of this review brings together the latest findings and highlights the translational significance of these developments.

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“…Many of its edges changed from strong positive correlations to strong negative correlations among genes. CTSG is a well-established therapeutic target for both AML and ALL cancers (e.g., Jin et al, 2013 ; Khan et al, 2017 ). In a functional enrichment through EnrichR ( Kuleshov et al, 2016 ), cellular response to cytokine stimulus (GO:0071345) was significantly enriched (adjusted p -value < 0.01) among the genes within ALL_24.…”

Section: Resultsmentioning

confidence: 99%

Comparing Statistical Tests for Differential Network Analysis of Gene Modules

et al. 2021

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Genes often work together to perform complex biological processes, and “networks” provide a versatile framework for representing the interactions between multiple genes. Differential network analysis (DiNA) quantifies how this network structure differs between two or more groups/phenotypes (e.g., disease subjects and healthy controls), with the goal of determining whether differences in network structure can help explain differences between phenotypes. In this paper, we focus on gene co-expression networks, although in principle, the methods studied can be used for DiNA for other types of features (e.g., metabolome, epigenome, microbiome, proteome, etc.). Three common applications of DiNA involve (1) testing whether the connections to a single gene differ between groups, (2) testing whether the connection between a pair of genes differs between groups, or (3) testing whether the connections within a “module” (a subset of 3 or more genes) differs between groups. This article focuses on the latter, as there is a lack of studies comparing statistical methods for identifying differentially co-expressed modules (DCMs). Through extensive simulations, we compare several previously proposed test statistics and a new p-norm difference test (PND). We demonstrate that the true positive rate of the proposed PND test is competitive with and often higher than the other methods, while controlling the false positive rate. The R package discoMod (differentially co-expressed modules) implements the proposed method and provides a full pipeline for identifying DCMs: clustering tools to derive gene modules, tests to identify DCMs, and methods for visualizing the results.

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Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target

Cited by 21 publications

References 52 publications

Rapid Assessment of Functional Avidity of Tumor-Specific T Cell Receptors Using an Antigen-Presenting Tumor Cell Line Electroporated with Full-Length Tumor Antigen mRNA

Rapid Assessment of Functional Avidity of Tumor-Specific T Cell Receptors Using an Antigen-Presenting Tumor Cell Line Electroporated with Full-Length Tumor Antigen mRNA

Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer

Comparing Statistical Tests for Differential Network Analysis of Gene Modules

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