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Cancer Research Oct 2020Identification of tumor-specific cell surface antigens has proven challenging, as the vast majority of tumor-associated antigens are also expressed in normal tissues. In...
Identification of tumor-specific cell surface antigens has proven challenging, as the vast majority of tumor-associated antigens are also expressed in normal tissues. In mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, is incurable, and can be categorized into three histologic subtypes: epithelioid, biphasic, and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counterselection on normal cells and identified a panel of human antibodies that bind all subtypes of mesothelioma, but not normal mesothelium. One of the antibodies, M25, showed high specificity against an antigen we identify here as ALPPL2. IHC on normal human tissues found that ALPPL2 is expressed only on placental trophoblasts, but not on any other normal tissues. This significant tissue specificity and broad tumor type coverage suggest that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, an ALPPL2-targeted antibody-drug conjugate was developed and demonstrated potent and specific tumor killing and against both epithelioid and sarcomatoid mesothelioma. Thus, ALPPL2 belongs to a rare class of cell surface antigens classified as truly tumor specific and is well suited for therapy development against ALPPL2-expressing tumors. SIGNIFICANCE: These findings identify ALPP2 as a true tumor-specific cell surface antigen whose tissue specificity enables the development of novel therapies.
Topics: Alkaline Phosphatase; Animals; Antigens, Surface; Antineoplastic Agents, Immunological; CHO Cells; Cell Line, Tumor; Cricetulus; Epitopes; Female; GPI-Linked Proteins; Humans; Immunoconjugates; Immunoglobulin G; Male; Mesothelioma, Malignant; Mice, Inbred NOD; Molecular Targeted Therapy; Xenograft Model Antitumor Assays
PubMed: 32868383
DOI: 10.1158/0008-5472.CAN-20-1418 -
Journal of Biochemistry Sep 2019Signal enhancing systems have been introduced to enable detection of cell surface antigens by flow cytometry. Cell surface antigens are important targets that describe... (Review)
Review
Signal enhancing systems have been introduced to enable detection of cell surface antigens by flow cytometry. Cell surface antigens are important targets that describe the function and lineage of cells. Although flow cytometry is an effective tool for analysing cell surface antigens, this technique has poor sensitivity, which prohibits the detection of many important antigens on cell membranes. Thus, signal amplification is essential for developing practical tools for evaluating cell surface antigens by flow cytometry. Using a bright fluorophore or fluorescent polymer incorporated into antibodies is a straightforward strategy to improve flow cytometry sensitivity but may affect the functional characteristics of the labelled antibody. In contrast, enzymatic signal amplification is a more practical and efficient strategy to improve sensitivity that should not affect antibody activity. Although enzymatic signal amplification still has a number of drawbacks, this approach is a promising strategy to analyse cell surface antigens.
Topics: Antibodies; Antigens, Surface; Flow Cytometry; Fluorescent Dyes; Humans; Polymers
PubMed: 31251348
DOI: 10.1093/jb/mvz052 -
Blood Cells, Molecules & Diseases 2002Neutrophil surface molecules function in part as biological sensors. Surface antigens undergo several changes during neutrophilic maturation to accommodate the cell's... (Review)
Review
Neutrophil surface molecules function in part as biological sensors. Surface antigens undergo several changes during neutrophilic maturation to accommodate the cell's function. Surface antigens may appear with neutrophilic maturation, such as CD16b, CD35, and CD10; disappear with maturation, such as CD49d and CD64; be maintained during maturation, such as CD32, CD59, and CD82; or disappear with maturation but reappear after neutrophilic extravasation, such as CD49b. This article reviews the alterations in surface antigen expression during normal neutrophilic granulopoiesis.
Topics: Antigens, CD; Antigens, Surface; Cell Differentiation; Hematopoiesis; Humans; Neutrophils
PubMed: 12064921
DOI: 10.1006/bcmd.2002.0513 -
ASN Neuro 2022Enteric glia regulate gut functions in health and disease through diverse interactions with neurons and immune cells. Intracellular localization of traditional markers...
Enteric glia regulate gut functions in health and disease through diverse interactions with neurons and immune cells. Intracellular localization of traditional markers of enteric glia such as GFAP, s100b, and Sox10 makes them incompatible for studies that require antigen localization at the cell surface. Thus, new tools are needed for probing the heterogeneous roles of enteric glia at the protein, cell, and functional levels. Here we selected several cell surface antigens including Astrocyte Cell Surface Marker 2 (ACSA2), Cluster of differentiation 9 (CD9), lysophosphatidic acid receptor 1 (LPAR1), and Proteolipid protein 1 (PLP1) as potential markers of enteric glia. We tested their specificity for enteric glia using published single-cell/-nuclei and glia-specific translating mRNA enriched transcriptome datasets, immunolabeling, and flow cytometry. The data show that ACSA2 is a specific marker of mucosal and myenteric glia while other markers are suitable for identifying all subpopulations of enteric glia (LPAR1), glia and immune cells (CD9), or are not suitable for cell-surface labeling (PLP1). These new tools will be useful for future work focused on understanding specific glial functions in health and disease.This study identifies astrocyte cell surface antigen 2 as a novel marker of myenteric glia in the intestine. This, in combination with other markers identified in this study, could be used for selective targeting of enteric glia.
Topics: Animals; Antigens, Surface; Astrocytes; Colon; Mice; Neuroglia; Neurons
PubMed: 35593118
DOI: 10.1177/17590914221083203 -
Methods in Molecular Biology (Clifton,... 2017Larger extracellular vesicles, microparticles (MPs) or microvesicles (MVs), especially their acquisition and characterization by flow cytometry (FACS), is increasingly...
Larger extracellular vesicles, microparticles (MPs) or microvesicles (MVs), especially their acquisition and characterization by flow cytometry (FACS), is increasingly in focus of clinical/translational research efforts. Several laboratories have shown that MPs/MVs might be suitable for the diagnosis and predicting prognosis in various diseases including cancer. However, FACS staining of larger extracellular vesicles (EVs) can be difficult and results potentially in false positive and inconsistent data interpretation. Despite that FACS equipment is well maintained and the operators have ample experience, a reliable and for larger EVs optimized staining protocol is missing. Here, we aim to close that gap and provide a working multi-antibody staining protocol for larger EVs isolated from human serum samples. We describe in detail the needed steps as currently done in our laboratory. Staining is demonstrated exemplarily for multi-antibody mix including CD147 , a potential cancer marker if applied in combination with other MP/MV surface markers.
Topics: Antigens, Surface; Biomarkers; Extracellular Vesicles; Flow Cytometry; Humans; Staining and Labeling
PubMed: 28828658
DOI: 10.1007/978-1-4939-7253-1_16 -
Nature Jan 1981The fusion of mononucleate myoblast cells into multinucleate myotubes (myogenesis) has often been studied as a model system of terminal cellular differentiation....
The fusion of mononucleate myoblast cells into multinucleate myotubes (myogenesis) has often been studied as a model system of terminal cellular differentiation. Although cell-surface changes during myogenesis have attracted much attention and a variety of surface antigens including the nicotinic cholinergic receptor, acetylcholinesterase and muscle lectins have been shown to be present on muscle cells, a detailed identification of markers specific to the various cell types has not been attempted. This is mainly because fibroblasts are a major contaminating cell type in primary muscle cultures and these cells have no known distinctive cell-surface antigen(s). For instance, surface fibronectin has been used to distinguish fibroblasts in the rat peripheral nervous system in vitro but has proved ineffective in the human muscle cell system. In addition, Lesley and Lennon found that Thy-1 antigen was present on myoblasts but not myotubes of the rat L6 muscle cell line and primary cultures. However, Thy-1 antigen is also present on rat fibroblasts. Thus, unequivocal identification of the major mononucleate cell types in muscle cultures, fibroblasts and myoblasts has not been possible. We report here the use of two surface antigens, Thy-1 and a muscle-specific antigen recognized by a monoclonal antibody, to identify unambiguously the four major types of cells present in human muscle cultures and to propose a model of cell-surface differentiation during human myogenesis.
Topics: Antigens, Surface; Cell Differentiation; Cell Fusion; Cell Membrane; Cells, Cultured; Clone Cells; Fibroblasts; Humans; Mitosis; Muscles; T-Lymphocytes
PubMed: 6969855
DOI: 10.1038/289060a0 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Apr 2021B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar... (Review)
Review
B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar to those with childhood B-ALL, the rate of long-term disease-free survival (DFS) rate is significantly lower, once recurrence, the remission rate of routine chemotherapy is low and the prognosis is so poor. Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.
Topics: Adult; Antigens, CD19; Antigens, Surface; B-Lymphocytes; Burkitt Lymphoma; Child; Humans; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell
PubMed: 33812446
DOI: 10.19746/j.cnki.issn.1009-2137.2021.02.055 -
Nihon Rinsho. Japanese Journal of... Jun 1996Leukemic cells as well as normal blood cells possess several antigens on their cell surfaces. By detecting these cell-specific molecules using monoclonal antibodies and... (Review)
Review
Leukemic cells as well as normal blood cells possess several antigens on their cell surfaces. By detecting these cell-specific molecules using monoclonal antibodies and flow cytometry, these immunological methods can be applied to both clinical and basic tumor studies. The analysis of cell surface markers has been applied in the diagnosis and the management of hematological disorders such as leukemias and lymphomas and it has become to be utilized as the routine work in many laboratories. Such analysis has been particularly useful in lymphocytic leukemias due to the ability of this method to classify lymphocyte subtypes, as well as specify their developmental origin. Importance is that, with this information, it is possible to determine expected clinical prognosis, to recommend treatment options and to judge treatment efficacy.
Topics: Antigens, Surface; Biomarkers, Tumor; Humans; Leukemia, Lymphoid; Leukocytes
PubMed: 8691606
DOI: No ID Found -
International Journal For Parasitology Jan 1998As for any intracellular parasite, the surface of the Apicomplexan parasite Toxoplasma gondii must fulfil many functions including a role in attachment, signalling,... (Review)
Review
As for any intracellular parasite, the surface of the Apicomplexan parasite Toxoplasma gondii must fulfil many functions including a role in attachment, signalling, invasion, transport and interaction with the immune response of the host. In this review, we describe the current state of knowledge on the molecules that are found on the surface of the different developmental stages of this parasite and speculate as to how at least some of these multiple functions are fulfilled. Special emphasis is given to the growing family of surface antigens that are related to the tachyzoite-specific surface antigen 1. We conclude that the surface (of tachyzoites, at least) is both more and less complex than previously thought: there are more proteins present but their sequences suggest that the majority may share a similar overall structure typified by surface antigen 1.
Topics: Animals; Antigens, Protozoan; Antigens, Surface; Life Cycle Stages; Toxoplasma
PubMed: 9504330
DOI: 10.1016/s0020-7519(97)00182-3 -
Seminars in Cancer Biology Feb 2002The identification of tumor-associated antigens has suggested new possibilities for cancer therapy. However, multiple mechanisms may contribute to the ability of tumor... (Review)
Review
The identification of tumor-associated antigens has suggested new possibilities for cancer therapy. However, multiple mechanisms may contribute to the ability of tumor to escape antitumor immune responses. Tumor antigen heterogeneity, modulation of HLA expression and immune suppressive mechanisms may occur at any time during tumor cell progression, and can affect the outcome of therapeutic immune intervention. In particular, the appearance of altered HLA class I phenotypes during tumor development may have important biological and medical implications due to the role of these molecules in T and NK cell functions. Exhaustive tumor tissue studies are necessary before deciding whether a particular patient is suitable for inclusion in T cell-based immunotherapy protocols.
Topics: Antigens, Surface; Humans; Immunotherapy; Neoplasms
PubMed: 11926407
DOI: 10.1006/scbi.2001.0406