Clinical study of Camrelizumab combined with Bevacizumab and DC-CIK in the treatment of advanced colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2692527 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Background: Combinations of Dendritic and Cytokine-induced Killer Cells (DC-CIK) and Cytokine-induced Killer Cells (CIK) treatment may enhance the immune response and stop cancer cells from growing. The investigators suppose that DC-CIK combined with CIK treatment will improve the prognosis of advanced solid tumors.
Objective: Phase II clinical trial to investigate the efficacy of concurrent chemotherapy with DC-CIK and CIK treatment in patients with treatment-refractory solid tumors.
Study treatment:
Patients in group A will receive 4 cycles of CIK treatments and 4 cycles of DC-CIK treatments within 8 months. Patients in group B will have no immunotherapy . chemotherapy are available in both groups.
| 2236267 | ecrin-mdr-crc
Project description:The purpose of this study is to evaluate the efficacy of dendritic and cytokine-induced killer cells (DC-CIK) for colorectal cancer (CRC).
| 2143734 | ecrin-mdr-crc
Project description:Stage III colorectal cancer constitutes more than half of the colorectal patients, and the prognosis does not improve much recently although varies of adjuvant drugs have been tried. DC-CIK immunotherapy has been proved to improve survival in cancer patients, but its role in stage III colorectal cancer patients stains unclear. The investigators study will focus on the efficacy and safety of DC-CIK immunotherapy plus chemotherapy in the adjuvant treatment of stage III colorectal cancer, compared with chemotherapy alone.
| 2187838 | ecrin-mdr-crc
Project description:Cytokine Induced Killer (CIK) cells are heterogeneous ex vivo expanded T lymphocytes with mixed T-NK phenotype and endowed with a wide MHC-unrestricted antitumor activity against both solid and hematologic malignancies. CIK cells can be easily ex vivo expanded up to clinical relevant rates from circulating peripheral blood mononuclear cells (PBMC), according to a standard protocol involving timed stimulation with IFN- γ (day 0), Ab-antiCD3 OKT3 (day 1) and IL-2 (from day 1 to the end). Nowadays literature provides scanty information on cytokines, chemokines and growth factors secreted by CIK cells. A comprehensive molecular profiling of CIK cells is needed to complete the knowledge of their biologic and functional features. In this perspective we performed a gene expression profile analysis of basal PBMC and ex vivo expanded CIK cells generated from 3 patients with histologic confirmed Gastrointestinal Stromal Tumors (GIST). The principal component analysis (PCA) shows that the CIK cell samples clustered together and were clearly separated from PBMC ones. First, we checked the mRNA expression levels of secreted proteins and we found a significant upregulation of GM-CSF, IL-5, IL-13, and IFN-γ in CIK cells. Moreover, IL-1Ra, IL-1β, IL-6, IL-10, IL-15, IL-8, Eotaxin and MCP-1 are downregulated in CIK cells if compared to PBMC. Noteworthy, among differentially expressed genes (DEGs) we identified other secreted molecules that are upregulated in patient-derived CIK cells, which can contribute to their tumor killing activity: GZMA, GZMB, GZMK, PRF1, IL-32, and LTA. Furthermore, to better characterize the CIK cell phenotype, we studied the surface antigen expression. As expected, we found the downregulation of several myeloid differentiation markers (CD14, CD9, CD93, CSF2RA, CSF2RB, EPB41L3, Receptors for Fc fragments of immunoglobulins, ITGAX, MCEMP1, and TREM1) and B-cell antigens (CD19, CD24, CD79A, CXCR5, and MS4A1). Moreover, microarray data confirmed the upregulation in CIK cells of well-known surface antigens, like CD3D, CD3G, IL2Ra, IL2RG, CD226/DNAM1, ITGAL/LFA-1, KLRK1/NKG2D, NCR3/NKp30, and TRAIL/TNFSF10. Next, in order to identify differentially expressed pathways during CIK cells maturation, we performed a functional analysis by using Ingenuity Pathway Analysis (IPA) software. Among inactivated functions in CIK cells, we found chemotaxis of myeloid cells, phagocytosis, migration of granulocytes and engulfment of leukocytes. Noteworthy, functional gene categories as proliferation of cells, cell death of lymphocytes, cell death of mononuclear leukocytes, apoptosis of B lymphocytes, and quantity of CD4+ T-lymphocytes resulted activated, in agreement with the selection and expansion of CIK cell precursors induced by in vitro treatment of PBMC. Finally, IPA analysis predicted as activated categories cytotoxicity of lymphocytes, cytotoxicity of cells, and cytotoxicity of natural killer cells. In particular, genes involved in cytotoxic mechanism of CIK cells like NCR3/NKp30, KLRK1/NKG2D, TRAIL/TNFSF10, CD226/DNAM1, CD244, CD69, CD96, GZMA, GZMB, PRF1 are differentially expressed. With this work we highlighted previously unknown secretory properties and provided for the first time a comprehensive molecular characterization of CIK cells, opening the possibility to operate on secretory level to improve CIK cell cytotoxic activity against tumors.
2023-04-07 | GSE97581 | GEO
Project description:Dr. Christopher Contag lab's aim is to, investigate the molecular interactions that underlie CIK cell homing from the bloodstream to tumor tissue using a combination of gene expression profiling, flow cytometry, and in vivo molecular imaging. Collectively, these proposed experiments will define the repertoire of molecules employed in CIK cell recognition of the tumor vasculature and guide the development of improved CIK cell therapies for use in cancer patients. A promising new direction in cancer therapy is the use of cytokine-induced killer (CIK) cells as broadly active tumoricidal agents. CIK cells derive from blood samples stimulated ex vivo, and these activated immune cells are capable of recognizing and destroying a plethora of tumor targets in vivo. In fact, CIK cells have demonstrated efficacy in clinical trials to treat patients with hepatoma, renal cell cancer, and hematological malignancies. Despite the remarkable clinical promise of this therapy, little is known about the mechanisms that govern CIK cell migration to tumor tissue in vivo. Understanding the trafficking patterns of these potent immune cells is of critical importance to advancing their use in humans. I aim to investigate the molecular interactions that underlie CIK cell homing from the bloodstream to tumor tissue using a combination of gene expression profiling, flow cytometry, and in vivo molecular imaging. Collectively, these proposed experiments will define the repertoire of molecules employed in CIK cell recognition of the tumor vasculature and guide the development of improved CIK cell therapies for use in cancer patients. RNA from three groups (1,2,3) were sent to Microarray Core E. Group one samples: Splenocytes were obtained from BALB/c mice, and the T cells were isolated using a negative isolation kit (magnetic bead separation). For group 2 and 3 samples: The isolated splenocytes were treated with IFN-gamma overnight. The cells were then added to anti-CD3 coated flasks and stimulated with IL-2. Fresh IL-2 was added to the media every 3 days, and the cells were harvested 12 days post-isolation. The RNA was labeled and hybridized to Glyco_v3 arrays.
2011-04-29 | E-GEOD-28940 | biostudies-arrayexpress
Project description:Circulating tumor cells (CTCs) have the potential to provide a surrogate for’real-time biopsy’ of tumor biological activity. Enumeration and molecular characterization of CTCs in colorectal cancer could play an important role in diagnosis, predicting the risk for tumor recurrence, and providing novel target therapy biomarkers. In view of these facts, the investigators wanted to demonstrate the value of multiparameter flow cytometry in detecting human tumor cells of colorectal cancer in normal peripheral blood after cryosurgery with or without dendritic cell(DC)-cytokine-induced killers(CIK) treatment, and the investigators also compared the specificity with reverse transcriptase polymerase chain reaction (RT-PCR) method.
| 2190499 | ecrin-mdr-crc
Project description:Dr. Christopher Contag lab's aim is to, investigate the molecular interactions that underlie CIK cell homing from the bloodstream to tumor tissue using a combination of gene expression profiling, flow cytometry, and in vivo molecular imaging. Collectively, these proposed experiments will define the repertoire of molecules employed in CIK cell recognition of the tumor vasculature and guide the development of improved CIK cell therapies for use in cancer patients. A promising new direction in cancer therapy is the use of cytokine-induced killer (CIK) cells as broadly active tumoricidal agents. CIK cells derive from blood samples stimulated ex vivo, and these activated immune cells are capable of recognizing and destroying a plethora of tumor targets in vivo. In fact, CIK cells have demonstrated efficacy in clinical trials to treat patients with hepatoma, renal cell cancer, and hematological malignancies. Despite the remarkable clinical promise of this therapy, little is known about the mechanisms that govern CIK cell migration to tumor tissue in vivo. Understanding the trafficking patterns of these potent immune cells is of critical importance to advancing their use in humans. I aim to investigate the molecular interactions that underlie CIK cell homing from the bloodstream to tumor tissue using a combination of gene expression profiling, flow cytometry, and in vivo molecular imaging. Collectively, these proposed experiments will define the repertoire of molecules employed in CIK cell recognition of the tumor vasculature and guide the development of improved CIK cell therapies for use in cancer patients.
2011-04-29 | GSE28940 | GEO
Project description:Interventions: 1:Camrelizumab, Cetuximab, and chemotherapeutics.;2:Camrelizumab, Cetuximab and chemotherapeutics.
Primary outcome(s): ORR
Study Design: Non randomized control
| 2688526 | ecrin-mdr-crc
Project description:CD3+/CD56+ Natural killer (NK) cell-like T-cells (NKT-like cells) represent <5% of blood lymphocytes, display a cytotoxic phenotype, and can kill various cancers. NKT-like cells can be expanded ex vivo into cytokine-induced killer (CIK) cells, however this therapeutic cell product has had mixed results against hematological malignancies in clinical trials. The aim of this study was to determine if NKT-like cells mobilized during acute cycling exercise could be used to generate more potent anti-tumor CIK cells from healthy donors. An acute exercise bout increased NKT-like cell numbers in blood 2-fold. Single cell RNA sequencing revealed that exercise mobilized NKT-like cells have an upregulation of genes and transcriptomic programs associated with enhanced anti-tumor activity, including cytotoxicity, cytokine responsiveness, and migration. Exercise, however, did not augment the ex vivo expansion of CIK cells or alter their surface phenotypes after 21-days of culture. CIK cells expanded at rest, during exercise (at 60% and 80% VO2max) or after (1h post) were equally capable of killing leukemia, lymphoma, and multiple myeloma target cells with and without cytokine (IL-2) and antibody (OKT3) priming in vitro. We conclude that acute exercise in healthy donors mobilizes NKT-like cells with an upregulation of transcriptomic programs involved in anti-tumor activity, but does not augment the ex vivo expansion of CIK cells.
2022-09-12 | GSE212740 | GEO
Project description:In this study, the resistant and susceptible monoclonal CIK cell lines were first established which would be the ponderable research models for the nosogenesis mechanism of the hemorrhagic disease. C1 (CIK cells), R2 (resistant cells) and S3 (susceptible cells) samples were carried out RNA-Seq, MeDIP-Seq and small RNA-Seq by the next-generation sequencing strategy, bioinformatics analysis as well as experimental verification. It was discovered that the aboriginality of CIK cells were gravitated to the susceptible trait. And the discrepancies between resistance and susceptibility against GCRV could primarily attribute to antioxidant activity, cell killing activity and cell proliferation regulation. Here we comprehensively present the profiling and characteristics of DNA methylation and microRNA in the resistant and susceptible CIK cells and proposed that high mCHH methylation distribution might be a characteristic modulator in C. idella. What’s more, a series of genes modulated by DNA methylation or microRNA were designated as potential biomarkers for the resistance breeding. This study laid the foundation and opened novel avenues for nosogenesis research on hemorragic disease of C. idella.
2016-09-28 | GSE87405 | GEO