Search results for "C2"
showing 10 items of 879 documents
Trial Watch: Adoptively transferred cells for anticancer immunotherapy
2017
IF 7.719; International audience; Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with th…
A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets.
2018
International audience; NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCR(B6C14R) strain. Ly5.1(C14R) NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46(C14R) in 293T cells showed that NKp46 protein trafficking to the cell surface …
Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer ste…
2018
Despite marked advancements in its treatment, breast cancer is still the second leading cause of cancer death in women, due to relapses and distal metastases. Breast cancer stem cells (CSCs), are a cellular reservoir for recurrence, metastatic evolution and disease progression, making the development of novel therapeutics that target CSCs, and thereby inhibit metastases, an urgent need. We have previously demonstrated that the cystine-glutamate antiporter xCT (SLC7A11), a protein that was shown to be overexpressed in mammary CSCs and that plays a key role in the maintenance of their redox balance, self-renewal and resistance to chemotherapy, is a potential target for mammary cancer immunoth…
Evolution of melanoma cross-resistance to CD8⁺ T cells and MAPK inhibition in the course of BRAFi treatment
2018
The profound but frequently transient clinical responses to BRAFV600 inhibitor (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies. Multiple clinical trials combining BRAFi and immunotherapy are under way to further enhance therapeutic responses. However, to which extent BRAFV600 inhibition may affect melanoma immunogenicity over time remains largely unknown. To support the development of an optimal treatment protocol, we studied the impact of prolonged BRAFi exposure on the recognition of melanoma cells by T cells in different patient models. We demonstrate that autologous CD8+ tumor-infiltrating lymphocytes (TILs) efficiently recognized short-term (3, 7 days) BRAF…
A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refract…
2018
ABSTRACT We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): e…
Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.
2018
Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261. Moreover, SB28 shows features of a poorly immunogenic tumor, with low MHC-I expression and modest CD8(+) T-cell infiltration, suggest…
Toma de decisiones en el paciente diagnosticado de tumor cerebral. A propósito de un caso clínico
2007
Pilar.Barreto@uv.es Justificación: La decisión sobre la alternativa terapéutica más conveniente, que corresponde al paciente asesorado por el equipo sanitario, se hace especialmente difícil en casos del mal pronóstico. Pacientes: Paciente joven con tumor cerebral, reintervenido en diversas ocasiones, al que se detecta una recidiva. Resultados: En contra de la opinión del equipo multidisciplinar, el paciente decide someterse a una reintervención, falleciendo a los cuatro meses presentando una calidad de vida aceptable. Conclusiones: Se plantea la necesidad, a través de un counselling adecuado, de permitir que el paciente escoja el resultado clínico preferido tras la transmisión clara de las …
Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1&al…
2023
Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in cytosolic…
IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia
2021
Simple Summary Although the prognosis of acute lymphoblastic leukemia (ALL) has improved significantly during the past decades, ALL remains a major cause of pediatric cancer mortality, and more accurate risk-stratification is required. We investigated IGF2BP3, which has previously been associated with aggressive cancers, and found high and subtype-specific expression of IGF2BP3 in B-cell ALL, that was associated with good outcome in high-risk patients. Results suggest that IGF2BP3 could be useful to improve stratification and prognosis of B-ALL. Abstract The oncofetal protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) belongs to a family of RNA-binding proteins involved i…
Monoclonal antibodies against components of the classical pathway of complement.
1989
Activation of the classical pathway of complement involves several binding and enzymatic cleavage processes. Binding and enzymatic activation results in the appearance of new structures in the individual components. This report describes the different activation steps for C1q, C1r, C1s, C4 and C2 and summarizes monoclonal antibodies reported so far which recognize either conserved epitopes or activation-dependent epitopes with particular emphasis on neoepitopes occurring during the activation cascade.