Search results for "immunotherapy"
showing 10 items of 830 documents
Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages
2020
free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupl…
Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia
2020
Background. Haematological and non-haematological malignancies are able to escape the host immune by the capacity to hijack the immune check-points. Several immune check-point molecules are known, such as T cell immunoglobulin mucin-3 (TIM-3), cytotoxic T-cell antigen-4 (CTLA-4), programmed death-1 (PD-1) with its ligand PD-L1 and others.1 The function of these immune check-points is to prevent the damage resulting from an excessive activation of the immune response in the setting of chronic antigenic stimulation, thus leading to autoimmune phenomena, as proved in knock-out mice models. PD-1 is normally present on activated T lymphocytes membrane, acting as a negative costimulatory receptor…
Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic…
2018
ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in m…
Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
2019
Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (N = 496) and a validation set (DKTK MASTER cohort, N = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately re-analyzed. APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV-negative HNSCC samples. An APOBEC-enriched, HPV-nega…
Fluorescent Probes for Ecto-5′-nucleotidase (CD73)
2020
[Image: see text] Ecto-5′-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes to an immunosuppressive microenvironment. In the present study we designed and synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity and high selectivity based on N(6)-benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure. Fluorescein was attached to the benzyl residue via different linkers resulting in PSB-19416 (14b, K(i) 12.6 nM) and PSB-18332 (14a, K(i) 2.98 nM) as fluorescent high-affinity probes for CD73. These compounds …
Aminobisphosphonates as new weapons for gammadelta T Cell-based immunotherapy of cancer.
2008
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …
Gene Therapy With a High-Affinity Single-Chain p53-Specific TCR Mediates Potent Anti-Tumor Response Without Inducing Gvhd In Vivo
2013
Abstract The adoptive transfer of tumor-reactive cells is a promising approach in the treatment of human malignancies, but the challenge of isolating T cells with high-avidity for tumor antigens in each patient has limited its widespread application. Using HLA-A2.1 transgenic mice, we have demonstrated the feasibility of T-cell receptor (TCR) gene transfer into T cells to circumvent self-tolerance to the widely expressed human p53(264-272) tumor-associated antigen and developed approaches to generate high-affinity CD8-independent TCR. However, a safety concern of TCR gene transfer is the risk of pairing between introduced and the naturally expressed endogenous TCR chains, resulting in the g…
T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice.
2013
Background & Aims Antiviral agents suppress hepatitis B virus (HBV) replication but do not clear the infection. A strong effector T-cell response is required to eradicate HBV, but this does not occur in patients with chronic infection. T cells might be directed toward virus-infected cells by expressing HBV-specific receptors and thereby clear HBV and help to prevent development of liver cancer. In mice, we studied whether redirected T cells can engraft after adoptive transfer, without prior T-cell depletion, and whether the large amounts of circulating viral antigens inactivate the transferred T cells or lead to uncontrolled immune-mediated damage. Methods CD8 + T cells were isolated from m…
In Vitro Priming to Tumor-Associated Proteins
1997
Cancer can be cured in mice by adoptive transfer of T cells specific for the malignant cells or by vaccination to tumor-specific antigens. The application of immunotherapy to the treatment of human cancer hinges on the identification of human tumor antigens to which specific immunity can be elicited.
p53 Immunotherapy of Cancer
2012
Mutation and overexpression of the p53 tumor suppressor protein are the most common genetic alterations in human cancers. Peptides derived from non-mutated (wild type, wt) and mutated p53-molecules, processed and presented in the context of major histocompatibility complex (MHC) molecules by tumor cells for T-cell recognition, could serve as broad targets for cancer immunotherapy. Isolating p53-reactive T lymphocytes in healthy donors or patients has been hampered by the fact that most individuals display a peripheral p53-reactive T-cell repertoire that is devoid of high-avidity MHC class I-restricted cytotoxic T lymphocytes (CTL). Only low-avidity T lymphocytes are left due to self-toleran…