Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE226619 | GEO | 2023/03/06
REPOSITORIES: GEO
Similar Datasets
Project description:Here we report a humanized clear cell renal cell carcinoma (ccRCC) orthotopic NSG-SGM3 mouse model (hccRCC-NSG-SGM3) with reconstituted human lymphocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) bearing human ccRCC skrc-59 cells under the kidney capsule. Human leukocyte antigen (HLA) matched CD34+ HSCs were used for the humanization to reduce T cell alloreactivity against skrc-59 human ccRCC cells. Tumors were collected and sorted for CD45+ tumor infiltrated leukocytes (TILs) to profile the tumor microenvironment (TME) in hccRCC-NSG-SGM3. By comparing to patient data from prospective clinical trials of the anti-PD-1 monoclonal antibody (mAb) nivolumab in advanced ccRCC, the results demonstrated that the CD45+ TILs from hccRCC-NSG-SGM3 reconstitutes most CD45+ cell types, including NK cells, dendritic cells, exhausted CD8 T cells, regulatory T cells (Tregs), that are observed in advanced ccRCC patient TME. Furthermore, Anti-carbonic anhydrase IX (CAIX) G36 immune restoring (IR) chimeric antigen receptor (CAR) T cells secreting PD-L1 targeted immune checkpoint inhibitor (ICI) mAb (G36-PDL1) exhibited superior tumor control compared to G36 CAR-T cells with anti-SARS mAb (G36-SARS) and anti-BCMA A716 CAR-T cells with anti-PD-L1 mAb (A716-PDL1). In addition, G36-PDL1 CAR-T cells restored active anti-tumor immunity at tumor site uncovered by 10X genomics single cell RNA sequencing (scRNA-seq) and single cell T cell receptor sequencing (scTCR-seq).
2024-01-25 | GSE210664 | GEO
Project description:This study is a pilot study to determine whether patients with TNFα excess have decreased calcium absorption in response to calcitriol (1,25-dihydroxyvitamin D, the active form of vitamin D) compared to normal controls. This initial pilot study is being done to determine if it is feasible to conduct a study where TNFα could be blocked (e.g., by anti-TNFα therapy such as Enbrel or Remicade) to improve vitamin D dependant calcium absorption and thus bone health.
| 2036554 | ecrin-mdr-crc
Project description:We have developed a monoclonal antibody (mAb) C7 that reacts with Als3p and enolase present in Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of mAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in presence of a subinhibitory concentration of mAb C7 (12.5 µg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with mAb C7. Of these, 28 were found to be up-regulated and 21 down-regulated. The categories of up-regulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the down-regulated genes (8/21). Results were validated by real time PCR. Since these effects resembled those found under iron-limited conditions, the activity of mAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking TPK1 gene, and TPK2 to a lesser extent were less sensitive to the candidacidal effect of mAb C7. FeCl3 or hemin at concentrations ≥ 7.8µM reversed the candidacidal effect of mAb C7 on C. albicans, on a concentration dependent manner. The results presented in this study provide evidence that the candidacidal effect of mAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans.
2010-12-11 | GSE25969 | GEO
Project description:We have developed a monoclonal antibody (mAb) C7 that reacts with Als3p and enolase present in Candida albicans cell wall and exerts three anti-Candida activities: candidacidal activity and inhibition of both adhesion and filamentation. To investigate the mode of action of mAb C7 on fungal viability, we examined changes in the genome-wide gene expression profile of C. albicans grown in presence of a subinhibitory concentration of mAb C7 (12.5 µg/ml) by using microarrays. A total of 49 genes were found to be differentially expressed upon treatment with mAb C7. Of these, 28 were found to be up-regulated and 21 down-regulated. The categories of up-regulated genes with the largest number of variations were those involved in iron uptake or related to iron homeostasis (42.86%), while the energy-related group accounted for 38.10% of the down-regulated genes (8/21). Results were validated by real Time PCR. Since these effects resembled those found under iron-limited conditions, the activity of mAb C7 on C. albicans mutants with deletions in key genes implicated in the three iron acquisition systems described in this yeast was also assessed. Only mutants lacking TPK1 and TPK2 genes were less sensitive to the candidacidal effect of mAb C7. FeCl3 or hemin at concentrations ≥ 7.8µM reversed the candidacidal effect of mAb C7 on C. albicans, on a concentration dependent manner. The results presented in this study provide evidence that the candidacidal effect of mAb C7 is related to the blockage of the reductive iron uptake pathway of C. albicans. A saturated culture of C. albicans grown overnight was diluted to an optical density at 600 nm of approximately 0.1 and divided in two aliquots. One of them was used untreated as control and the second one was treated with a subinhibitory concentration (12.5 µg/ml) of monoclonal antibody C7 . Both cultures were incubated for 18 h at 37ºC before harvesting cells. Antibody added and control samples were obtained each time. The experiment was repeated once. Dye-swap technique was used for hybridization and four arrays were analyzed to compare the expresion of over six thousands genes in response to antibody C7.
2010-12-11 | E-GEOD-25969 | biostudies-arrayexpress
Project description:CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer. The study compared gene expression profiles between human CRC cells HT29 before and after expression of 1 and 2 shRNA vectors directed at the human CD24 gene, GFP control gene, HT29 cells and Colo357, human pancreatic cancer cells, before and after the inhibition of the CD24 molecule using 72h treatment with anti-CD24 monoclonal antibodies.
2009-03-07 | E-GEOD-15102 | biostudies-arrayexpress
Project description:CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer.
2009-03-07 | GSE15102 | GEO
Project description:Transcriptional profiling of glioblastoma orthotopic xenografts Descriptive experiment, comparison of 39 glioblastoma tumors as orthotopic xenografts
2012-07-10 | E-GEOD-38814 | biostudies-arrayexpress
Project description:Human antibody responses to AM/LAM are heterogenous and knowledge of reactivity to specific glycan epitopes at the monoclonal level is limited. Using novel glycan arrays, we characterized a very high affinity monoclonal antibody P1AM25 to AM/LAM, determined this mAb recognized distinct glycan epitopes from other anti-AM/LAM mAbs reported.
2023-11-08 | GSE218873 | GEO
Project description:To assess the preclinical utility and functional mechanism of intraperitoneal anti-CX3CL1 mAb therapy in the skin and lung fibrosis, sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) model mice were analyzed by RNA-sequencing assays.
2024-05-03 | GSE227285 | GEO
Project description:Transcriptional profiling of glioblastoma orthotopic xenografts
2012-07-11 | GSE38814 | GEO