Search results for " cytotoxic"
showing 10 items of 315 documents
Chemical Characterization and Cytotoxic and Antioxidant Activity Evaluation of the Ethanol Extract from the Bulbs of Pancratium maritimun Collected i…
2023
P. maritimum L., belonging to the Amaryllidaceae family, is a species that grows on beaches and coastal sand dunes mainly on both sides of the Mediterranean Sea and Black Sea, the Middle East, and up to the Caucasus region. It has been largely investigated due to its several interesting biological properties. With the aim of providing new insights into the phytochemistry and pharmacology of this species, the ethanolic extract of the bulbs from a local accession, not previously studied, growing in Sicily (Italy), was investigated. This chemical analysis, performed by mono- and bi-dimensional NMR spectroscopy, as well as LC-DAD-MSn, allowed to identify several alkaloids, three of which were n…
Cellular and humoral immune responses against cancer: implications for cancer vaccines.
1991
The key issue in tumor immunology is to identify antigens as target structures for a cancer-selective immunological attack in the tumor-bearing host, resulting in tumor rejection. There is a growing detailed understanding of structural and regulatory gene alterations giving rise to candidate rejection antigens and peptides in tumor cells. As well as reviewing the development of new adjuvant and recombinant vector systems, new approaches are suggested for the construction of cancer vaccines.
Influence of different complement sources in apoptosis of B-CLL cells with rituximab
2004
Abstract Introduction: Rituximab (Rtx) is an anti-CD20 monoclonal antibody that is clinically active in B-cell chronic lymphocytic leukemia (B-CLL). In vitro and in vivo data indicate that Rtx mediates its biologic effect through multiple mechanisms including apoptosis, complement dependent cytotoxicity (CDC), and antibody dependent cellular cytotoxicity (ADCC). Objetive: To study in vitro sensitivity to apoptosis by Rtx of isolated cells obtained from B-CLL patients Binet stage A, in the presence of complement from different sources and correlate with CD20 and CD59 molecules expression. Methods: PBMCs were isolated from peripheral blood samples by centrifugation on a Ficoll/Hypaque gradien…
IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity
2014
Anti-EGFR monoclonal antibodies (mAb) like Cetuximab are commonly used for treatment of EGFR+ solid tumors mainly by exerting their therapeutic effect through inhibition of signal transduction. Additionally, IgG1 is a potent mediator of antibody-dependent cytotoxicity (ADCC). In case of the IgG1, Cetuximab induction of ADCC in vivo is controversially discussed. In our study, we investigated the efficiency of Cetuximab-mediated ADCC in a humanized mouse tumor model in vivo and analyzed the contribution of immunologic processes toward antitumor activity. Therefore, we used immunodeficient NOD/Scid mice transgenic for human MHC class I molecule HLA-A2 and adoptively transferred human HLA-A2+ P…
Abstract 2903: IMAB362, a novel first-in-class monoclonal antibody for treatment of pancreatic cancer
2014
Abstract Pancreatic ductal adenocarcinoma (PDAC), the most frequent subtype (>80%) of pancreatic cancer (PC) is characterized by a generally lethal progress within a short period of time after primary diagnosis. Despite high efforts, the treatment options are very limited and mainly of palliative nature. Therefore, we investigated whether IMAB362 might represent a potential treatment option in this patient population. IMAB362 is a highly potent and tumor-cell selective therapeutic antibody which is currently in clinical development in gastro-esophageal cancer (in phase II and IIb trials). IMAB362 is directed against the tight junction molecule CLDN18.2, a proliferation-promoting tran…
Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent e…
2012
2567 Background: MEHD is a novel dual-action human IgG1 antibody that blocks ligand binding to HER3 and EGFR, and elicits antibody-dependent cell-mediated cytotoxicity (ADCC). MEHD demonstrates single-agent activity in a broad panel of tumor models, including models resistant to anti-HER3 or anti-EGFR treatment alone. The objective of this analysis was to characterize the PK of MEHD associated with body weight (BW)-based dosing used in a phase I study in patients with epithelial tumors and to evaluate the potential for using fixed dosing in future studies. Methods: Preliminary non-compartmental and population PK analyses were performed using patient data from the dose-escalation stage [1, …
The GAIN-C study (BP25438): Randomized phase II trial of RG7160 (GA201) plus FOLFIRI, compared to cetuximab plus FOLFIRI or FOLFIRI alone in second-l…
2012
TPS3637 Background: GA201 is a novel, dual-acting, humanized, glycoengineered IgG1 anti-EGFR monoclonal antibody, with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity in combination with signal inhibition. GA201 demonstrates significantly enhanced in vitro/vivo activity compared to cetuximab (cet) both as a single agent and in combination with irinotecan, in both KRAS mutant and BRAF mutant models and promising clinical activity in ph I and neo-adjuvant trials (Paz Ares et al, JCO 2011) including KRAS mutant mCRC. A randomized ph II program was launched: one study in NSCLC and GAIN-C in mCRC (NCT01326000), which is presented here. Methods: Main inclusion criteria are prog…
Immuntherapie des Kolorektalkarzinoms - aktueller Stand und Perspektiven
2006
The specific immunotherapy of colorectal cancer initially revealed promising results. However, a significant clinical benefit for patients has still to be proven in phase III trails. In order to compare the different clinical approaches and early phase I - II studies, there is an urgent need for the establishment and acceptance of new standardized diagnostic tools for detecting and quantifying induced and clinical relevant immune responses in patients. Whether or not subgroups with a certain genetic background, such as specific HLA alleles, reveal a better benefit from tumour vaccinations needs to be further analysed. Currently, only two specific antibodies, targeting membraneous receptors …
Optimizing Tumor-Reactive γδT Cells for Antibody-Based Cancer Immunotherapy
2010
Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu+ breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent function…
Targeting a Specific Glycosylated Epitope of CD43 with a New Humanized Monoclonal Antibody for the Treatment of Pediatric and Adult T-Cell Acute Lymp…
2018
Abstract Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for about 20% of pediatric and adult ALL cases. Despite the use of intensive chemotherapy protocols, 25% of children and 50% of adult patients fail to respond or relapse. The 3-years prognosis for these patients is poor and novel treatment options are needed. The targeting of tumor-associated antigens by monoclonal antibodies (mAb) is among the most investigated immune-therapeutic strategies. Accordingly, we developed a new humanized mAb (hUMG1), directed against a heavy glycosylated epitope of CD43 which presents a high reactivity against T-ALL cells. Here we investigated the pre-clinical therapeutic activity and t…