Human NK cell-mediated direct and IgG-dependent cytotoxicity against xenogeneic porcine endothelial cells

Watier, Hervé; Guillaumin, Jean‐Maurice; Vallée, Isabelle; Thibault, Gilles; Gruel, Yves; Lebranchu, Yvon; Bardos, P.

doi:10.1016/s0966-3274(96)80050-5

Cited by 62 publications

(23 citation statements)

References 19 publications

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“…This reaction is mediated by the binding of anti-aGal antibodies from the recipient to aGal epitopes expressed on the xenograft and complement activation through the classic pathway (5). In addition, noncomplement fixing natural anti-aGal antibody induces antibodydependent cell-mediated cytotoxicity that initiates tissue damage in xenotransplants mediated by natural killer cells (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing α(1,3)-Galactosyl Epitopes

et al. 2005

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The hyperacute immune response in humans is a potent mechanism of xenograft rejection mediated by complementfixing natural antibodies recognizing A(1,3)-galactosyl epitopes (AGal) not present on human cells. We exploited this immune mechanism to create a whole cell cancer vaccine to treat melanoma tumors. B16 melanoma vaccines genetically engineered to express AGal epitopes (B16AGal) effectively treated preexisting s.c. and pulmonary AGal-negative melanoma (B16Null) tumors in the A(1,3)-galactosyltransferase knockout mouse model. T cells from mice vaccinated with B16AGal recognized B16Null melanoma cells measured by detection of intracellular tumor necrosis factor-A. We showed successful adoptive transfer of immunity to recipient mice bearing lung melanoma metastasis. Mice receiving lymphocytes from donors previously immunized with B16AGal had reduced pulmonary metastases. The transfer of lymphocytes from mice vaccinated with control vaccine had no effect in the pulmonary metastasis burden. This study unequivocally establishes for the first time efficacy in the treatment of preexisting melanoma tumors using whole cell vaccines expressing AGal epitopes. Vaccination with B16Agal induced strong long-lasting cell-mediated antitumor immunity extended to B16Null. These data formed the basis for the testing of this therapeutic strategy in human clinical trials currently under way. (Cancer Res 2005; 65(22): 10555-61)

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Section: Introductionmentioning

confidence: 99%

Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing α(1,3)-Galactosyl Epitopes

et al. 2005

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“…This rejection is mediated by complement that is activated as a result of anti-Gal binding to ␣-gal epitopes on the graft endothelial cells. However, even if complement activation is inhibited, xenografts are rejected because of binding of various effector cells with Fc␥ receptors (Fc␥R) (e.g., monocytes/macrophages, neutrophils, and NK cells) to the Fc portion of anti-Gal on xenograft cells and destruction of these cells by the antibody-dependent cell cytotoxicity mechanism (11,57). In addition, because of its effective interaction with Fc␥R, antiGal can opsonize tumor cells expressing ␣-gal epitopes for very effective uptake by various APC including macrophages and dendritic cells (DC) which express these receptors, thereby increasing the immunogenicity of tumor vaccines (13,28,33).…”

mentioning

confidence: 99%

Increased Immunogenicity of Human Immunodeficiency Virus gp120 Engineered To Express Galα1-3Galβ1-4GlcNAc-R Epitopes

Abdel-Motal

Wang

et al. 2006

J Virol

107

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The glycan shield comprised of multiple carbohydrate chains on the human immunodeficiency virus (HIV) envelope glycoprotein gp120 helps the virus to evade neutralizing antibodies. The present study describes a novel method for increasing immunogenicity of gp120 vaccine by enzymatic replacement of sialic acid on these carbohydrate chains with Gal␣1-3Gal␤1-4GlcNAc-R (␣-gal) epitopes. These epitopes are ligands for the natural anti-Gal antibody constituting ϳ1% of immunoglobulin G in humans. We hypothesize that vaccination with gp120 expressing ␣-gal epitopes (gp120 ␣gal ) results in in vivo formation of immune complexes with anti-Gal, which targets vaccines for effective uptake by antigen-presenting cells (APC), due to interaction between the Fc portion of the antibody and Fc␥ receptors on APC. This in turn results in effective transport of the vaccine to lymph nodes and effective processing and presentation of gp120 immunogenic peptides by APC for eliciting a strong anti-gp120 immune response. This hypothesis was tested in ␣-1,3-galactosyltransferase knockout mice, which produce anti-Gal. Mice immunized with gp120 ␣gal produced anti-gp120 antibodies in titers that were >100-fold higher than those measured in mice immunized with comparable amounts of gp120 and effectively neutralized HIV. T-cell response, measured by ELISPOT, was much higher in mice immunized with gp120 ␣gal than in mice immunized with gp120. It is suggested that gp120 ␣gal can serve as a platform for anti-Gal-mediated targeting of additional vaccinating HIV proteins fused to gp120 ␣gal , thereby creating effective prophylactic vaccines.

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“…Several seminal studies demonstrated in vitro the destruction of cells by complement mediated cytolysis (Good et al, 1992, Sandrin et al, 1993 or by Ab dependent cell mediated cytotoxicity (ADCC) (Galili, 1993;Watier et al, 1996) due to interaction of human anti-Gal Ab with -gal epitopes on pig cells or on monkey cells transfected with 1,3GT gene and thus expressing the -gal epitopes on their cell membrane.…”

Section: The Rejection Of Xenografts By the Anti-gal Abmentioning

confidence: 99%

Anti-Gal and Anti-Non Gal Antibody Barriers in Xenotransplantation

Galili¹

2012

Xenotransplantation

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Human NK cell-mediated direct and IgG-dependent cytotoxicity against xenogeneic porcine endothelial cells

Cited by 62 publications

References 19 publications

Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing α(1,3)-Galactosyl Epitopes

Effective Treatment of Preexisting Melanoma with Whole Cell Vaccines Expressing α(1,3)-Galactosyl Epitopes

Increased Immunogenicity of Human Immunodeficiency Virus gp120 Engineered To Express Galα1-3Galβ1-4GlcNAc-R Epitopes

Anti-Gal and Anti-Non Gal Antibody Barriers in Xenotransplantation

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