A cell surface antigen of the mouse related to xenotropic MuLv defined by naturally occurring antibody and monoclonal antibody. Relation to Gix G(rada1), G(aksl2) systems of MuLV-related antigens.

A new cell surface antigen of the mouse related to xenotropic murine leukemia virus (MuLV) is described. The antigen, designated G(erld), is defined by cytotoxic tests with the B6-x-ray-induced ERLD and naturally occurring antibody. G(erld) is distinct from all previously defined cell surface antigens. Monoclonal antibody with the same specificity has been developed. Inbred mouse strains are classified as G(erld)+ or G(erld)- according to the presence of absence of the antigen on lymphoid cells. G(erld)+ strains differ with regard to quantitative expression of G(erld) on normal thymocytes. The emergence of G(erld)+ tumors in G(erld)- strains indicates the presence of genes coding for the antigen even in strains not normally expressing the antigen. G(erld) has the characteristic of a differentiation antigen in normal mice. In G(erld)+ strains, high levels of the antigen are found on thymocytes with lower levels being detected on cells of spleen, lymph nodes and bone marrow. No G(erld) was detected in brain or kidney or on erythrocytes. The segregation ratios for G(erld) expression on thymocytes in backcross and F2 mice of crosses between G(erld)+ (B6, 129, and B6-Gix+) and G(erld)- (BALB/c) strains suggest that G(erld) expression is controlled by a single locus in B6, by two unlinked loci in 129, and by three unlinked loci in B6-Gix+ mice. Induction of the antigen by MuLV infection of permissive cells in vitro indicates that G(erld) is closely related to xenotropic and dualtropic MuLV; all xenotropic and dualtropic MuLV tested induced the antigen, whereas the majority of ecotropic and the two amphotropic MuLV failed to do so. As dualtropic MuLV are thought to be recombinants between ecotropic and xenotropic MuLV sequences, G(erld) coding by dualtropic MuLV may signify the contribution of the xenotropic part in the recombinational event. Serological and biochemical characterization indicates that G(erld) is related to the gp 70 component of the MuLV envelope. The relation of G(erld) to the previously defined gp 70-related cell surface antigens (Gix, G(rada), and G(aksl2) is discussed, particularly with regard to their characteristics as differentiation antigens, the genetic origin of dualtropic MuLV, and the leukemogenicity of MuLV.

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Genetics of cell-surface antigens: Regional mapping of three components of the human cell-surface antigen complex, Al, on chromosome 11

Somatic Cell Genetics ◽

10.1007/bf01542970 ◽

1977 ◽

Vol 3 (4) ◽

pp. 421-429 ◽

Cited By ~ 38

Author(s):

Fa-Ten Kao ◽

Carol Jones ◽

Theodore T. Puck

Keyword(s):

Cell Surface ◽

Surface Antigen ◽

Human Cell ◽

Surface Antigens ◽

Cell Surface Antigen ◽

Regional Mapping ◽

Chromosome 11 ◽

Cell Surface Antigens ◽

Antigen Complex ◽

Three Components

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ALPPL2 is a highly specific and targetable tumor cell surface antigen

10.1101/2020.01.07.898122 ◽

2020 ◽

Author(s):

Yang Su ◽

Xin Zhang ◽

Scott Bidlingmaier ◽

Christopher R. Behrens ◽

Nam-Kyung Lee ◽

...

Keyword(s):

Cell Surface ◽

Tumor Cell ◽

Surface Antigen ◽

Tissue Specificity ◽

Surface Antigens ◽

Cell Surface Antigen ◽

Cell Surface Antigens ◽

Normal Tissues ◽

Specific Tumor ◽

Therapy Development

AbstractIt has been challenging to identify tumor-specific cell surface antigens as the vast majority of tumor-associated antigens are also expressed by some normal tissues. In the course of our study on 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, incurable and categorized into three histological 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 counter-selection 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, and we hereby report the identification of the M25 antigen as ALPPL2. We performed immunohistochemistry on normal human tissues and found that ALPPL2 is expressed only on placental trophoblasts but not any other normal tissues. This exquisite tissue specificity and broad tumor type coverage suggests that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, we developed an ALPPL2-targeted antibody-drug conjugate and demonstrated potent and specific tumor killing in vitro and in vivo against both epithelioid and sarcomatoid mesothelioma. Thus ALPPL2 belongs to a rare class of cell surface antigens that can be said as being truly tumor specific and is well suited for therapy development against ALPPL2 expressing tumors.

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G(RADA1): a new cell surface antigen of mouse leukemia defined by naturally occurring antibody and its relationship to murine leukemia virus.

Journal of Experimental Medicine ◽

10.1084/jem.147.4.1089 ◽

1978 ◽

Vol 147 (4) ◽

pp. 1089-1105 ◽

Cited By ~ 20

Author(s):

Y Obata ◽

E Stockert ◽

P V O'Donnell ◽

S Okubo ◽

H W Snyder ◽

...

Keyword(s):

Cell Surface ◽

Solid Tumors ◽

Biochemical Characterization ◽

Leukemia Virus ◽

Mouse Strains ◽

Cell Surface Antigens ◽

Widespread Occurrence ◽

Normal Tissues ◽

Naturally Occurring

A new cell surface antigenic system of the mouse, designated G(RADA1), is described. The antigen is defined by cytotoxic tests with the A strain X-ray-induced leukemia RADA1 and naturally occurring antibody from random-bred Swiss mice and can be distinguished from all other serologically detected cell surface antigens of the mouse. Absorption tests indicate that G(RADA1) is present in the normal lymphatic tissue and leukemias of mouse strains with high spontaneous leukemia-incidence, e.g., AKR, C58, and C3H/Figge. Low leukemia-incidence strains, e.g., C57BL/6, BALB/c, and A lack G(RADA1) in their normal tissues, but a proportion of leukemias and solid tumors arising in these strains are G(RADA1)+. The relation of G(RADA1) to MuLV is shown by G(RADA1) appearance after MuLV infection of permissive cells in vitro; four of five N-tropic MuLV isolates, one of four B-tropic MuLV, and none of four xenotropic MuLV induce G(RADA1). Two MCF MuLV, thought to represent recombinants between N-ecotropic and xenotropic MuLV, also induce G(RADA1). Serological and biochemical characterization indicates that G(RADA1) is a type-specific determinant of the gp70 component of certain MuLV. The presence of natural antibody to RADA1 in various mouse strains and the emergence of G(RADA1)+ leukemias and solid tumors in mice of G(RADA1)- phenotype suggest widespread occurrence of genetic information coding for this antigen.

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Facilely synthesized polydopamine encapsulated surface-enhanced Raman scattering (SERS) probes for multiplex tumor associated cell surface antigen detection using SERS imaging

RSC Advances ◽

10.1039/c5ra12628b ◽

2015 ◽

Vol 5 (88) ◽

pp. 72369-72372 ◽

Cited By ~ 17

Author(s):

Changlong Sun ◽

Ling Zhang ◽

Ren Zhang ◽

Mingxia Gao ◽

Xiangmin Zhang

Keyword(s):

Cell Surface ◽

Raman Scattering ◽

Surface Antigen ◽

Surface Antigens ◽

Cell Surface Antigen ◽

Cell Surface Antigens ◽

Surface Enhanced ◽

Surface Enhanced Raman ◽

Enhanced Raman Scattering ◽

Sers Imaging

A novel SERS probes fabrication were studies and used for multiplex tumor associated cell surface antigens detection using SERS imaging.

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THE GIX SYSTEM

Journal of Experimental Medicine ◽

10.1084/jem.133.6.1334 ◽

1971 ◽

Vol 133 (6) ◽

pp. 1334-1355 ◽

Cited By ~ 138

Author(s):

Elisabeth Stockert ◽

Lloyd J. Old ◽

Edward A. Boyse

Keyword(s):

Cell Surface ◽

Surface Antigen ◽

De Novo ◽

Integration Site ◽

Inbred Mouse ◽

Lymphoid Cells ◽

Cell Surface Antigen ◽

Mouse Strains ◽

Good Prospect ◽

A Cell

This report concerns a cell surface antigen (GIX; G = Gross) which exhibits mendelian inheritance but which also appears de novo in cells that become productively infected with MuLV (Gross), the wild-type leukemia virus of the mouse. In normal mice, GIX is a cell surface allo-antigen confined to lymphoid cells and found in highest amount on thymocytes. Four categories of inbred mouse strains can be distinguished according to how much GIX antigen is expressed on their thymocytes. GIX- strains have none; in the three GIX+ categories, GIX3, GIX2, and GIX1, the amounts of GIX antigen present (per thymocyte) are approximately in the ratios 3:2:1. A study of segregating populations derived mainly from strain 129 (the prototype GIX3 strain) and C57BL/6 (the prototype GIX- strain) revealed that two unlinked chromosomal genes are required for expression of GIX on normal lymphoid cells. The phenotype GIX+ is expressed only when both genes are present, as in 129 mice. C57BL/6 carries neither of them. At one locus, expression of GIX is fully dominant over nonexpression (GIX fully expressed in heterozygotes). At the second locus, which is linked with H-2 (at a distance of 36.4 ± 2.7 units) in group IX (locus symbol GIX), expression is semidominant (50% expression of GIX in heterozygotes); gene order T:H-2:Tla:GIX. As a rule, when cells of GIX- mice or rats become overtly infected with MuLV (Gross), an event which occurs spontaneously in older mice of certain strains and which also commonly accompanies malignant transformation, their phenotype is converted to GIX+. This invites comparison with the emergence of TL+ leukemia cells in TL- mouse strains which has been observed in previous studies and which implies that TL- → TL+ conversion has accompanied leukemic transformation of such cells. So far the only example of GIX- → GIX+ conversion taking place without overt MuLV infection is represented by the occurrence of GCSA-:GIX+ myelomas in BALB/c (GCSA:GIX-) mice. Unlike the other Gross cell surface antigen described earlier, GCSA, which is invariably associated with MuLV (Gross) infection and never occurs in its absence, GIX antigen sometimes occurs independently of productive MuLV infection; for example, thymocytes and some leukemias of 129 mice are GCSA-:GIX+, and MuLV-producing sarcomas may be GCSA+:GIX-. The frequent emergence of cells of GIX+ phenotype in all mouse strains implies that the structural gene coding for GIX antigen is common to all mice. There is precedent for this in the TL system, in which two of the Tla genes in linkage group IX appear to be ubiquitous among mice, but are normally expressed only in strains of mice carrying a second (expression) gene. It is not yet certain whether either of the two segregating genes belongs to the MuLV genome rather than to the cellular genome. This leaves the question whether MuLV may have a chromosomal integration site still debatable. But there is a good prospect that further genetic analysis will provide the answer and so elucidate the special relationship of leukemia viruses to the cells of their natural hosts.

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