Search results for " cytotoxic"
showing 10 items of 315 documents
Self-adjuvanting synthetic antitumor vaccines from MUC1 glycopeptides conjugated to T-cell epitopes from tetanus toxoid.
2013
The T-helper epitope peptide P30 (green in the scheme) from tetanus toxoid was used as the immunostimulant in MUC1 glycopeptide antitumor vaccines and apparently also acts as a built-in adjuvant. P30-conjugated glycopeptide vaccines containing three glycans in the immunodominant motifs PDTRP and GSTAP induced much stronger immune responses and complement dependent cytotoxicity mediated killing of tumor cells when applied in plain PBS solution without complete Freund's adjuvant.
The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes.
1998
The disappointing clinical results of cancer immunotherapy of the past few decades have not diminished the optimism about the potential of the new generation of immunotherapeutic strategies towards treatment of malignant disease. Tremendous progress has been made over recent years in unveiling the molecular basis of antigen presentation and recognition by cytotoxic T lymphocytes (CTL). The molecular concepts that have emerged from these studies have led to the design of novel anticancer vaccines and CTL-based immunotherapeutics. This review is to highlight the current molecular insights of antigen presentation and CTL recognition/activation, and their impact on the rational design of therap…
Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario.
2015
Abstract: Introduction: The identification of cell membrane-bound molecules with a relevant role in cancer cell survival prompted the development of moAbs to block the related pathways. In the last few years, the number of approved moAbs for cancer treatment has constantly increased. Many of these drugs significantly improved the survival outcomes in patients with solid tumours. Areas covered: In this review, all the FDA-approved moAbs in solid tumours have been described. This is an update of moAbs available for cancer treatment nowadays in comparison with the moAbs approved until few years ago. The moAbs under development are also discussed here. Expert opinion: The research on cancer ant…
Generating p53-specific cytotoxic T lymphocytes by recombinant adenoviral vector-based vaccination in mice, but not man.
2002
Mutations and aberrant expression of the p53 tumor suppressor protein are the most frequent molecular alterations in human malignancy. Peptides derived from the wild-type (wt) p53 protein and presented by major histocompatibility complex (MHC) molecules for T lymphocyte recognition are believed to serve as universal tumor-associated antigens for cancer immunotherapy. We studied the immunogeneicity of a recombinant replication-defective adenoviral vector encoding human full-length wt p53 (rAd/hup53) in human leukocyte antigen (HLA)-A2K(b)-transgenic (Tg) mice and man. The generation of p53 epitope-specific cytotoxic T lymphocytes (CTLs) in p53-proficient and p53-deficient A2K(b)-Tg mice was …
The Role of Fc Receptors on the Effectiveness of Therapeutic Monoclonal Antibodies.
2021
Since the approval of the first monoclonal antibody (mAb) in 1986, a huge effort has been made to guarantee safety and efficacy of therapeutic mAbs. As of July 2021, 118 mAbs are approved for the European market for a broad range of clinical indications. In order to ensure clinical efficacy and safety aspects, (pre-)clinical experimental approaches evaluate the respective modes of action (MoA). In addition to antigen-specificity including binding affinity and -avidity, MoA comprise Fc-mediated effector functions such as antibody dependent cellular cytotoxicity (ADCC) and the closely related antibody dependent cellular phagocytosis (ADCP). For this reason, a variety of cell-based assays have…
Molecular Identification and Biochemical Characterization of Novel Marine Yeast Strains with Potential Application in Industrial Biotechnology
2022
Cell-based agriculture is an emerging and attractive alternative to produce various food ingredients. In this study, five strains of marine yeast were isolated, molecularly identified and biochemically characterized. Molecular identification was realized by sequencing the DNA ITS1 and D1/D2 region, and sequences were registered in GenBank as Yarrowia lipolytica YlTun15, Rhodotorula mucilaginosa RmTun15, Candida tenuis CtTun15, Debaryomyces hansenii DhTun2015 and Trichosporon asahii TaTun15. Yeasts showed protein content varying from 26% (YlTun15) to 40% (CtTun15 and DhTun2015), and essential amino acids ranging from 38.1 to 64.4% of the total AAs (CtTun15-YlTun15, respectively). Lipid conte…
HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis.
1993
Ankylosing spondylitis and seronegative spondylarthropathies such as Reiter's syndrome and reactive arthritis are strongly associated with HLA-B27. However, the mechanisms by which HLA-B27 is involved in disease susceptibility and pathogenesis are unknown. If the disease association is a consequence of HLA-B27's physiological function in antigen presentation, the disease should be mediated by cytotoxic T lymphocytes (CTLs) that recognise bacterial or self peptides presented by HLA-B27. Proof of this arthritogenic peptide model requires isolation of B27-restricted CD8 T cells from arthritic joints of patients with spondylarthropathies. An important question is whether "arthritogenic" bacteri…
HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segm…
1996
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes wit…
Bacteria-specific cytotoxic CD8+ T cells: a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies.
1994
The term seronegative spondylarthropathies is used for an entity of rheumatic syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel disease) which are strongly associated with the MHC class I molecule HLA-B27. However, the mechanisms whereby HLA-B27 confers disease susceptibility have so far remained unknown. There is strong evidence that gut inflammation and infection with gram-negative bacteria play a role in the induction of B27-associated disease. HLA-B27, like other MHC class I molecules, physiologically binds antigenic peptides in its binding groove and presents them to CD8+ T lymph…
Enterobacterial Antigens with Tropism for Joint Structures and HLA-B27=Restricted Cytotoxic T-Cells in Reactive Arthritis
1995
In reactive arthritis (ReA), sterile synovitis is an immunological sequela following gastrointestinal or urogenital infection with facultatively intracellular bacteria (Yersinia, Salmonella, Shigella, Chlamydia). It is widely accepted now that the development of arthritis is closely related to the persistance of bacteria or bacterial antigens in extraarticular mucosal or lymphoid tissues (i.e. gut mucosa, gut associated lymphoid tissue, genitourinary mucosa); however, it is still unclear which host mechanisms are responsible for the poorer elimination of arthritis-causing microorganisms in those ReA patients. Bacterial components are also camed to the joints where they can be demonstrated i…