A Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC)
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasm Metastasis,Stage Iii Colorectal Cancer,Colorectal Neoplasms,Colorectal Cancer Liver Metastasis
PROVIDER: 2348838 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:The main purpose of this research is to verify the safety of CEA targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.
| 2182785 | ecrin-mdr-crc
Project description:Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.
| 2210681 | ecrin-mdr-crc
Project description:Adoptive transfer of chimeric antigen receptor (CAR)-T cells is expected to become the first line of treatment for multiple malignancies, following the enormous success of anti-CD19 therapies. However, their mechanism of action is not fully understood, and clear guidelines for the design of safe and efficient receptors are missing. We hereby describe a systematic analysis of the CAR “signalosome” in human primary T cells. Two CAR designs were compared: a second-generation (PSCA2) and a third-generation (PSCA3) anti-PSCA CAR. Phosphorylation events triggered by CAR-mediated recognition of target cells were quantified by mass spectrometry.
2019-11-07 | PXD007086 | Pride
Project description:Adoptive transfer of chimeric antigen receptor (CAR)-T cells is expected to become the first line of treatment for multiple malignancies, following the enormous success of anti-CD19 therapies. However, their mechanism of action is not fully understood, and clear guidelines for the design of safe and efficient receptors are missing. We hereby describe a systematic analysis of the CAR “interactome” in human primary T cells, which allowed us to identify molecular traits that influence CAR-T cell efficacy. Interactome analysis was based on immunoprecipitation of CARs followed by protein identification by mass spectrometry.
2019-11-07 | PXD007085 | Pride
Project description:The direct integration of chimeric-antigen-receptor (CAR) T cell with allogeneic hematopoietic cell transplantation (allo-HCT) carries the risk of graft-versus-host disease (GVHD) induction by allogeneic CAR-T cells. Based on our past experiments, it has been shown that post-transplantation cyclophosphamide (PTCy) prevents GVHD induction by other cell infusions after T-cell-replete MHC-haploidentical murine allo-HCT models. In this study, we investigated whether CAR-T cells, given in a similar manner in the same MHC-haploidentical murine allo-HCT model, could safely exert anti-tumor effects. We showed that anti-CD19 CAR-T cells administered early after (day +5 of transplant) or prior to (day 0 of transplant) PTCy for allo-HCT cleared leukemia without toxicity or GVHD exacerbation. Using next generation single-cell RNA sequencing approaches, we demonstrated that in comparison to CAR-T cells infused early after PTCy (day +5), CAR-T cells infused prior to PTCy (day 0) exhibited transcriptional changes consistent with increased CD4+ T-cell activation and CD8+ T-cell cytotoxicity.
2022-10-09 | GSE214788 | GEO
Project description:Adoptive cell therapy, a subset of cancer immunotherapy, is collection of therapeutic approaches which aim to redirect the immune system by reprogramming patient T-cells to target antigenic molecules differentially and specifically expressed in certain cancers. One promising immunotherapy technique is CAR T-cell therapy, where cancer cells are targeted through the expression a chimeric antigen receptor (CAR), a synthetic trans- membrane receptor that functionally compensates for the T-cell receptor (TCR) but targets a tumor associated antigen on the cancer cell surface. While CAR T-cell therapy is promising with two clinically approved second-generation CARs (Kymriah and Yescarta), few studies have investigated the mechanism of signal propagation in T-cells and no studies have investigated the potential signaling response in the target cells. To gain further insight to CAR-based signaling, we stimulated third generation CD19 CAR-expressing Jurkat T-cells by co-culture with SILAC labeled CD19HI Raji B-cells and used two phosphoenrichment strategies coupled with liquid chromatography-tandem mass spec- trometry (LC-MS/MS) to detect and analyze global phosphorylation changes in both cell populations. Analysis of the phosphopeptides originating from the CD19-CAR T cells revealed an increase in many phosphorylation events necessary for canonical TCR signaling. We also observed for the first time a significant decrease in B-cell receptor- related phosphopeptide abundance in CD19HI Raji B-cells after co-culture with CD19-targetted CAR T-cells.
2022-01-28 | PXD028109 | Pride
Project description:Chimeric antigen-receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) lead to high response rates in myeloma, but most patients experience recurrent disease. We combined several high-dimensional approaches to study tumor/immune cells in the tumor microenvironment of myeloma patients pre- and post-BCMA-specific CAR T therapy. A lower diversity of pre-therapy T-cell-receptor (TCR) repertoire, presence of hyperexpanded clones with an exhaustion phenotype, and BAFF+PD-L1+ myeloid cells in the marrow correlated with shorter progression-free survival (PFS) following CAR T therapy. In contrast, longer PFS was associated with increased proportion of CLEC9A+ dendritic cells (DCs), and CD27+TCF1+ T cells with diverse T-cell receptors, followed by emergence of T cells expressing marrow-residence genes. Residual tumor cells at initial response express stem-like genes and tumor recurrence in patients with long PFS was associated with emergence of new dominant clones. These data illustrate dynamic interplay between endogenous T, infused CAR T, myeloid/DC and tumor compartments that impacts durability of response following CAR T therapy in myeloma.
2022-08-11 | GSE210079 | GEO
Project description:Murine chimeric antigen receptor transduced T cells (CAR-T cells) deficient in perforin recapitulate hemophagocytic lymphohistiocytosis (HLH)-like toxicities occuring in human CAR-T recipients. We used microarray to describe gene expression profiles of wild-type and perforin-deficient CAR-T cells.
2020-10-07 | GSE130929 | GEO
Project description:The aim of the study was to compare and contrast cytokine production by CD4+ chimeric antigen receptor + T-cells and putative myeloid derived suppressor cell populations (CD11b+Gr-1 hi and lo) in the spleens of Balb/c mice which had received a transfer of CD19 specific second-generation CAR T-cells 56 days previously following cyclophosphamide pre-conditioning. Splenocytes from four individual mice were pooled, incubated with antibodies to CD4, CD34 (CAR), CD11b, Gr-1 and sorted using flow cytometric cell sorting for CD4+CD34+, Gr-1 and the negative cell fraction. Total RNA was isolated and samples loaded in duplicate in the array. Data was normalized to global expression levels.
2014-02-06 | E-GEOD-54696 | biostudies-arrayexpress
Project description:This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.
| 2348111 | ecrin-mdr-crc