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  1. Article ; Online: Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.

    Nabel, Katherine G / Clark, Sarah A / Shankar, Sundaresh / Pan, Junhua / Clark, Lars E / Yang, Pan / Coscia, Adrian / McKay, Lindsay G A / Varnum, Haley H / Brusic, Vesna / Tolan, Nicole V / Zhou, Guohai / Desjardins, Michaël / Turbett, Sarah E / Kanjilal, Sanjat / Sherman, Amy C / Dighe, Anand / LaRocque, Regina C / Ryan, Edward T /
    Tylek, Casey / Cohen-Solal, Joel F / Darcy, Anhdao T / Tavella, Davide / Clabbers, Anca / Fan, Yao / Griffiths, Anthony / Correia, Ivan R / Seagal, Jane / Baden, Lindsey R / Charles, Richelle C / Abraham, Jonathan

    Science (New York, N.Y.)

    2022  Volume 375, Issue 6578, Page(s) eabl6251

    Abstract: Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We ... ...

    Abstract Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.
    MeSH term(s) Angiotensin-Converting Enzyme 2/chemistry ; Angiotensin-Converting Enzyme 2/metabolism ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; BNT162 Vaccine/immunology ; Betacoronavirus/immunology ; COVID-19/immunology ; COVID-19/virology ; Cross Reactions ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Epitopes ; Evolution, Molecular ; Humans ; Immune Evasion ; Models, Molecular ; Mutation ; Polysaccharides/analysis ; Protein Binding ; Protein Domains ; Receptors, Coronavirus/chemistry ; Receptors, Coronavirus/metabolism ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Viral Pseudotyping
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Polysaccharides ; Receptors, Coronavirus ; Spike Glycoprotein, Coronavirus ; spike glycoprotein, SARS-CoV ; spike protein, SARS-CoV-2 ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; BNT162 Vaccine (N38TVC63NU)
    Language English
    Publishing date 2022-01-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abl6251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Metastatic melanomas express inhibitory low affinity fc gamma receptor and escape humoral immunity.

    Cohen-Solal, Joel F G / Cassard, Lydie / Fournier, Emilie M / Loncar, Shannon M / Fridman, Wolf Herman / Sautès-Fridman, Catherine

    Dermatology research and practice

    2010  Volume 2010, Page(s) 657406

    Abstract: Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of primary cutaneous ... ...

    Abstract Our research, inspired by the pioneering works of Isaac Witz in the 1980s, established that 40% of human metastatic melanomas express ectopically inhibitory Fc gamma receptors (FcgammaRIIB), while they are detected on less than 5% of primary cutaneous melanoma and not on melanocytes. We demonstrated that these tumoral FcgammaRIIB act as decoy receptors that bind the Fc portion of antimelanoma IgG, which may prevent Fc recognition by the effector cells of the immune system and allow the metastatic melanoma to escape the humoral/natural immune response. The FcgammaRIIB is able to inhibit the ADCC (antibody dependent cell cytotoxicity) in vitro. Interestingly, the percentage of melanoma expressing the FcgammaRIIB is high (70%) in organs like the liver, which is rich in patrolling NK (natural killer) cells that exercise their antitumoral activity by ADCC. We found that this tumoral FcgammaRIIB is fully functional and that its inhibitory potential can be triggered depending on the specificity of the anti-tumor antibody with which it interacts. Together these observations elucidate how metastatic melanomas interact with and potentially evade humoral immunity and provide direction for the improvement of anti-melanoma monoclonal antibody therapy.
    Language English
    Publishing date 2010-06-28
    Publishing country Egypt
    Document type Journal Article
    ZDB-ID 2548952-5
    ISSN 1687-6113 ; 1687-6105
    ISSN (online) 1687-6113
    ISSN 1687-6105
    DOI 10.1155/2010/657406
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Fc gamma receptors.

    Cohen-Solal, Joël F G / Cassard, Lydie / Fridman, Wolf-Herman / Sautès-Fridman, Catherine

    Immunology letters

    2004  Volume 92, Issue 3, Page(s) 199–205

    MeSH term(s) Animals ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Agents/pharmacology ; Autoimmunity/immunology ; Humans ; Immunoglobulin G/immunology ; Neoplasms/drug therapy ; Neoplasms/immunology ; Receptors, IgG/immunology ; Rituximab
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Murine-Derived ; Antineoplastic Agents ; Immunoglobulin G ; Receptors, IgG ; Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2004-04-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 445150-8
    ISSN 1879-0542 ; 0165-2478
    ISSN (online) 1879-0542
    ISSN 0165-2478
    DOI 10.1016/j.imlet.2004.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Modulation of tumor growth by inhibitory Fc(gamma) receptor expressed by human melanoma cells.

    Cassard, Lydie / Cohen-Solal, Joël F G / Galinha, Annie / Sastre-Garau, Xavier / Mathiot, Claire / Galon, Jérôme / Dorval, Thierry / Bernheim, Alain / Fridman, Wolf H / Sautès-Fridman, Catherine

    The Journal of clinical investigation

    2002  Volume 110, Issue 10, Page(s) 1549–1557

    Abstract: The efficacy of anti-tumor IgG reflects the balance between opposing signals mediated by activating and inhibitory Fc(gamma) receptors (Fc(gamma)Rs) expressed by effector cells. Here, we show that human malignant melanoma cells express the inhibitory low- ...

    Abstract The efficacy of anti-tumor IgG reflects the balance between opposing signals mediated by activating and inhibitory Fc(gamma) receptors (Fc(gamma)Rs) expressed by effector cells. Here, we show that human malignant melanoma cells express the inhibitory low-affinity Fc(gamma) receptor Fc(gamma)RIIB1 in 40% of tested metastases. When melanoma cells were grafted in nude mice, a profound inhibition of Fc(gamma)RIIB1 tumor growth that required the intracytoplasmic region of the receptor was observed. IgG immune complexes (ICs) may be required for this inhibition, since sera from nude mice bearing tumors contained IgG that decreased the proliferation of Fc(gamma)RIIB1-positive cells in vitro, and tumor development of Fc(gamma)RIIB1-positive melanoma lines was not inhibited in antibody-defective severe combined immunodeficiency (SCID) mice. Passive immunization of SCID mice with anti-ganglioside G(D2) antibody resulted in significant inhibition of growth of Fc(gamma)RIIB1-positive tumors in an intracytoplasmic-dependent manner. Altogether, these data suggest that human melanoma cells express biologically active inhibitory Fc(gamma)RIIB1, which regulates their development upon direct interaction with anti-tumor antibodies. Therefore, Fc(gamma)R expression on human tumors may be one component of the efficacy of antibody-mediated therapies, and Fc(gamma)R-positive tumors could be the most sensitive candidates for such treatments.
    MeSH term(s) Animals ; Antibodies, Neoplasm/blood ; Cell Division ; Humans ; Immunization, Passive ; In Vitro Techniques ; Melanoma/immunology ; Melanoma/pathology ; Melanoma/secondary ; Melanoma/therapy ; Mice ; Mice, Nude ; Mice, SCID ; Neoplasm Transplantation ; Receptors, IgG/chemistry ; Receptors, IgG/genetics ; Receptors, IgG/metabolism ; Transfection ; Transplantation, Heterologous ; Tumor Cells, Cultured
    Chemical Substances Antibodies, Neoplasm ; Receptors, IgG
    Language English
    Publishing date 2002-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI15454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Selective expression of inhibitory Fcgamma receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular response.

    Cassard, Lydie / Cohen-Solal, Joel F G / Fournier, Emilie M / Camilleri-Broët, Sophie / Spatz, Alain / Chouaïb, Salem / Badoual, Cécile / Varin, Audrey / Fisson, Sylvain / Duvillard, Pierre / Boix, Charlotte / Loncar, Shannon M / Sastre-Garau, Xavier / Houghton, Alan N / Avril, Marie-Françoise / Gresser, Ion / Fridman, Wolf H / Sautès-Fridman, Catherine

    International journal of cancer

    2008  Volume 123, Issue 12, Page(s) 2832–2839

    Abstract: During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is ...

    Abstract During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (FcgammaR) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the FcgammaRIIB1, an inhibitory isoform of FcgammaR. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of FcgammaRIIB is restricted to melanoma and is acquired during tumor progression. We show that FcgammaRIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of FcgammaRIIB. Using experimental mouse models, we demonstrate that expression of FcgammaRIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify FcgammaRIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to FcgammaR-dependent innate effector responses.
    MeSH term(s) Animals ; Biomarkers, Tumor/analysis ; Cell Line, Tumor ; Disease Progression ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; Immunoglobulin G/immunology ; Immunohistochemistry ; Melanoma/immunology ; Melanoma/secondary ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Receptors, IgG/analysis ; Skin Neoplasms/immunology ; Skin Neoplasms/pathology
    Chemical Substances Biomarkers, Tumor ; Fc gamma receptor IIB ; Immunoglobulin G ; Receptors, IgG
    Language English
    Publishing date 2008-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218257-9
    ISSN 1097-0215 ; 0020-7136
    ISSN (online) 1097-0215
    ISSN 0020-7136
    DOI 10.1002/ijc.23870
    Database MEDical Literature Analysis and Retrieval System OnLINE

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