Vaccines prepared with sialyl-Tn and sialyl-Tn trimers using the 4-(4-maleimidomethyl)cyclohexane-1-carboxyl hydrazide linker group result in optimal antibody titers against ovine submaxillary mucin and sialyl-Tn-positive tumor cells

1999 ◽  
Vol 48 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Govindaswami Ragupathi ◽  
Lisa Howard ◽  
Sarah Cappello ◽  
R. Rao Koganty ◽  
Dongxu Qiu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Linker Group ◽  
Antibody Titers ◽  
Ovine Submaxillary Mucin ◽  
Sialyl Tn

scholarly journals Development of a novel target module redirecting UniCAR T cells to Sialyl Tn-expressing tumor cells

2018 ◽  
Vol 8 (9) ◽  
Author(s):  
L. R. Loureiro ◽  
A. Feldmann ◽  
R. Bergmann ◽  
S. Koristka ◽  
N. Berndt ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Novel Target ◽  
Target Module ◽  
Sialyl Tn

scholarly journals Siglec-15 recognition of sialoglycans on tumor cell lines can occur independently of sialyl Tn antigen expression

Glycobiology ◽  
2020 ◽  
Author(s):  
Gavuthami Murugesan ◽  
Viviana G Correia ◽  
Angelina S Palma ◽  
Wengang Chai ◽  
Chunxia Li ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cell Lines ◽  
Antigen Expression ◽  
Mapk Signaling ◽  
Breast Cancer Cell Lines ◽  
Cross Linking ◽  
Monocytic Cell ◽  
Immunosuppressive Microenvironment ◽  
Sialyl Tn Antigen ◽  
Sialyl Tn

Abstract Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors, which plays an important role in osteoclast development and function. It is also expressed by tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-β. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-β secretion following co-culture of Siglec-15-expressing monocytic cell lines with tumor cells expressing sTn or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages.

Circulating Antibodies to ALK Inversely Correlat with Relapse Risk and Circulating Tumor Cells in Children and Adolescents with ALK-Positive Anaplastic Large Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2831-2831
Author(s):  
Karen Pulford ◽  
Christine Damm-Welk ◽  
Birgit Burkhardt ◽  
Martin Zimmerman ◽  
Alfred Reiter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Autoantibody Response ◽  
Antibody Titers ◽  
Circulating Antibodies ◽  
Large Cell Lymphoma ◽  
Alk Positive

Abstract Tumour-associated antigens (TAAs) recognised by patients’ immune systems may be of prognostic relevance and also represent new immunotherapeutic targets. Circulating antibodies and T-cell responses to the TAA anaplastic lymphoma kinase (ALK) have been detected in patients with ALK-positive anaplastic large cell lymphoma (ALCL) (Pulford et al. Blood2000, 96:1605–7; Ait-Tahar et al. Int J Cancer2006, 118:688–95; Cancer Res2007, 65:1891–901). Their exact significance with regard to prognosis is, however, unclear at present. In contrast, and unusually for non-Hodgkin’s lymphoma, low numbers of circulating tumor cells (CTCs) expressing nucleophosmin (NPM)-ALK-transcripts at diagnosis in bone marrow or blood confers an unfavourable prognosis (Damm-Welk et al. Blood2007, 110:670–7). The current study was performed to address whether there was any correlation between the magnitude of the autoantibody response to ALK with prognosis and the levels of CTCs at diagnosis in a cohort of uniformly treated children and adolescents with ALK-positive ALCL for whom full clinical data was available. The anti-ALK-antibody titers were analyzed in initial serum or plasma samples from 86 patients and copies of NPM-ALK in initial bone marrow (n=61) and/or blood samples (n=53). The children were treated according to the NHL-BFM95 and ALCL99 trials carried out between 1996 and 2006. Antibody titers against ALK and copies of NPM-ALK were measured using ALK transfectants and quantitative RT-PCR as previously described (Pulford et al. Blood2000, 96:1605–7; Damm-Welk et al. Blood2007, 110:670–7). Circulating antibodies to ALK were detected in 80/86 (93%) of patients studied. The titers ranged between 1/50 and ≥1/60750. The median follow-up of the patients was 4.6 years (range 1.4–10.4 years). Antibody titers <1/60750, detected in 61 patients (71%), significantly correlated with advanced stage, mediastinal or visceral involvement. The 5 year event free survival rate (pEFS) of 25 patients with antibody titres ≥1/60750 was 88+/− 0.06% compared to 51+/−0.07% for 61 patients with titres less than 1/60750 (p<.003). Among those patients mounting an antibody response, higher antibody titers were significantly associated with lower cumulative incidence of relapses (CI-R): 17 patients with a titer between 1/50 and <1/2025 had a CI-R of 74±12% compared to a CI-R of 32±8% for 38 patients with titers between 1/2025 and <1/60750 and a CI-R of 12±7% for 25 patients with titers ≥1/60750 (p<.001). There was a significant inverse correlation between the magnitude of antibody titers and CTCs in 61 patients studied for the presence of both autoantibodies and CTC in bone marrow. None of the 20 patients with a high antibody titer (≥1/60750) had more than 10 copies NPM-ALK/104 copies ABL in bone marrow compared to 13 of 41 patients with lower antibody titers (p=.003). Comparison of antibody titers with CTCs in peripheral blood led to a similar grouping. In conclusion, the current study shows, for the first time, that the magnitude of the autoantibody response to ALK is inversely correlated with the relapse risk and disease dissemination in ALK-positive ALCL. Our results, therefore, provide clinical evidence that a strong immune response to ALK may control the progression of ALCL supporting the possibility that CTCs are a secondary phenomenon due to a limited anti-tumor immune response. These results also support the use of ALK as an immunotherapeutic target in ALCL.

scholarly journals Monoclonal Antibodies Recognising Sialyl-Tn: Production and Application to Immunochemistry

1994 ◽  
Vol 12 (3) ◽  
pp. 175-186 ◽  
Author(s):  
Peter L. Devine ◽  
Geoffrey W. Birrell ◽  
Rachel J. Quin ◽  
Paul W. Shield
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibodies ◽  
Normal Tissue ◽  
Sandwich Elisa ◽  
Ovarian Tumour ◽  
Tn Antigen ◽  
Bovine Submaxillary Mucin ◽  
Sialyl Tn Antigen ◽  
Ovine Submaxillary Mucin ◽  
Sialyl Tn

In order to develop reagents that can detect the exposed sialyl-Tn antigen (NeuAcα2,6GaINAcα 1-O-Ser/Thr) on tumour-associated mucins, we have prepared monoclonal antibodies (mabs 3C2 and 301, both IgM) against ovine submaxillary mucin (OSM; >98% of glycans as sialyl-Tn). These mabs showed strong reactivity with OSM and bovine submaxillary mucin (BSM; 50% of glycans as sialyl-Tn) but did not react with desialylated OSM or BSM. Sialic acid at I mg/ml did not significantly inhibit mab binding to OSM, suggesting that the linkage to GalNAc may be important for mab binding. 3C2 and 3D I also showed similar reactivity to sialyl-Tn reactive mab Bn.3, and detected Bn.3 capturedOSM in a sandwich ELISA. In Western blotting of mucus from a patient with a mucinous ovarian tumour, the mabs reacted with high molecular weight (>200 kDa) species. In immunohistochemistry, these mabs showed strong reactivity with most cancers of the colon, lung, and stomach, and also some tumours of the ovary and breast. There was only limited reactivity in normal tissue from these sites. The antibodies should be useful reagents for the detection of the sialyl-Tn antigen in human cancers.

Über die Antigenität eines chemisch induzierten neurogenen Sarkoms der Ratte [Antigenicity of a chemically induced neurogenic rat sarcoma—author's trans]

1980 ◽  
Vol 17 (4) ◽  
pp. 477-489
Author(s):  
H. Elling ◽  
D. Stavrou
Keyword(s):  
Tumor Cells ◽  
Cultured Cells ◽  
Fluorescent Antibody ◽  
Whole Body ◽  
Plexus Brachialis ◽  
Target Cells ◽  
Chemically Induced ◽  
S 100 ◽  
Antibody Titers

Antigenicity of a chemically induced neurogenic rat sarcoma A neurogenic sarcoma was induced in the plexus brachialis of a male Long-Evans rat by administration of N-methyl-N-nitrosourea in the drinking water. The tumor was established in vitro and designated 76LE-NS-369. Cells from tissue culture grew as tumors when isografted in young rats. 76LE-NS-369 cells did not react with antiserum directed against gliaspecific S-100 protein. We used the cultured cells as target cells, and found specific antibodies in the sera of tumor-bearing and immunized rats by indirect fluorescent antibody stain and a complement-dependent antibody-mediated microcytotoxicity assay. In immunization experiments, incubation of tumor cells with Vibrio cholerae neuraminidase yielded higher antibody titers than an antigen preparation with untreated cells. Incubation with neuraminidase enhanced the sensitivity of tumor cells to antibody and complement in vitro, whereas trypsinized cells showed complete loss of reactivity with autologous antisera. The specificity of antisera was tested by absorption with tumor, lyophilized rat whole body and rat nerve tissues.

Use of Protein a Conjugated to Peroxidase to Localize Immunoglobulin G in SSPE Ferret Brain

1982 ◽  
Vol 40 ◽  
pp. 350-351
Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar
Keyword(s):  
Immunoglobulin G ◽  
Human Disease ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Inflammatory Lesions ◽  
Sspe Virus ◽  
Specific Immunoglobulin ◽  
Antibody Titers ◽  
The Brain

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.

Membranous alterations in the cytoplasm and nucleus in a primitive neuroectodermal tumor of the brain

1978 ◽  
Vol 36 (2) ◽  
pp. 628-629
Author(s):  
C. N. Sun ◽  
C. Araoz ◽  
H. J. White
Keyword(s):  
Nuclear Envelope ◽  
Tumor Cells ◽  
Osmium Tetroxide ◽  
Primitive Neuroectodermal Tumor ◽  
Uranyl Acetate ◽  
Neuroectodermal Tumor ◽  
Annulate Lamellae ◽  
Lead Citrate ◽  
Thin Sections ◽  
The Brain

The ultrastructure of a cerebral primitive neuroectodermal tumor has been reported previously. In the present case, we will present some unusual previously unreported membranous structures and alterations in the cytoplasm and nucleus of the tumor cells.Specimens were cut into small pieces about 1 mm3 and immediately fixed in 4% glutaraldehyde in phosphate buffer for two hours, then post-fixed in 1% buffered osmium tetroxide for one hour. After dehydration, tissues were embedded in Epon 812. Thin sections were stained with uranyl acetate and lead citrate.In the cytoplasm of the tumor cells, we found paired cisternae (Fig. 1) and annulate lamellae (Fig. 2) noting that the annulate lamellae were sometimes associated with the outer nuclear envelope (Fig. 3). These membranous structures have been reported in other tumor cells. In our case, mitochondrial to nuclear envelope fusions were often noted (Fig. 4). Although this phenomenon was reported in an oncocytoma, their frequency in the present study is quite striking.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Ulcerogenic Tumors of the Pancreas

1968 ◽  
Vol 26 ◽  
pp. 186-187
Author(s):  
J. C. Garancis ◽  
J. F. Kuzma ◽  
S. D. Wilson ◽  
E. H. Ellison
Keyword(s):  
Endoplasmic Reticulum ◽  
Tumor Cells ◽  
Islet Cell ◽  
Disease Process ◽  
Central Core ◽  
Islet Cell Tumors ◽  
Opaque Zone ◽  
Granular Form ◽  
Zollinger Ellison Syndrome

It has been proposed that a gastrin-like hormone elaborated by non-beta islet tumors of the pancreas may be responsible for a fulminating ulcer diathesis. Subsequently, a potent gastric secretagogue was isolated from ulcerogenic tumors of the pancreas. This disease process is known now as “Zollinger-Ellison syndrome”.In our studies of two cases of Zollinger-Ellison syndrome, pancreatic lesions were identified as alpha islet cell tumors (Fig. 1). Tumor cells were fairly uniform. The sizes of the alpha granules were not significantly different, but their number and distribution varied greatly from one cell to another. Each granule consisted of a round, highly dense central core, separated from the limiting membrane by an opaque zone. The granular form of the endoplasmic reticulum was particularly prominent. Numerous mitochondria, round or elongated, were dispersed throughout the cytoplasm. Individual or clusters of lysosomes were observed in the majority of cells.

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