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000170228 1001_ $$aQuitt, Oliver$$b0
000170228 245__ $$aT cell engager antibodies enable T cells to control HBV infection and to target HBsAg-positive hepatoma in mice.
000170228 260__ $$a[S.l.]$$bWiley-Blackwell$$c2021
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000170228 500__ $$a2021 Nov;75(5):1058-1071
000170228 520__ $$aCurrent antiviral therapies control but rarely eliminate HBV, leaving chronic HBV carriers at risk of developing hepatocellular carcinoma (HCC). Lacking or dysfunctional virus-specific adaptive immunity prevents control of HBV and allows the virus to persist. Restoring antiviral T cell immunity could lead to HBV elimination and cure of chronically infected patients.We constructed bispecific T cell engager antibodies that are designed to induce antiviral immunity through simultaneous binding of HBV envelope proteins (HBVenv) on infected hepatocytes and CD3 or CD28 on T cells. T cell engager antibodies were employed in co-cultures with healthy donor lymphocytes and HBV-infected target cells. Activation of the T cell response was determined by detection of pro-inflammatory cytokines, effector function (by cytotoxicity) and antiviral effects. To study in vivo efficacy, immune-deficient mice were transplanted with HBVenv-positive and -negative hepatoma cells.The 2 T cell engager antibodies synergistically activated T cells to become polyfunctional effectors that in turn elicited potent antiviral effects by killing infected cells and in addition controlled HBV via non-cytolytic, cytokine-mediated antiviral mechanisms. In vivo in mice, the antibodies attracted T cells specifically to the tumors expressing HBVenv resulting in T cell activation, tumor infiltration and reduction of tumor burden.This study demonstrates that the administration of HBVenv-targeting T cell engager antibodies facilitates a robust T cell redirection towards HBV-positive target cells and provides a feasible and promising approach for the treatment of chronic viral hepatitis and HBV-associated HCC.T cell engager antibodies are an interesting, novel therapeutic tool to restore immunity in patients with chronic hepatitis B. As bispecific antibodies, they bind envelope proteins on the surface of the hepatitis B virus (HBV) and CD3 or CD28 on T cells. This way, they induce a potent antiviral and cytotoxic T cell response that leads to the elimination of HBV-positive cells. These bispecific T cell engager antibodies are exciting therapeutic candidates for chronic hepatitis B and HBV-associated hepatocellular carcinoma.
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000170228 650_7 $$2Other$$aT cell redirection
000170228 650_7 $$2Other$$aViral hepatitis
000170228 650_7 $$2Other$$abispecific T cell engager
000170228 650_7 $$2Other$$aimmunotherapy
000170228 7001_ $$aLuo, Shanshan$$b1
000170228 7001_ $$0P:(DE-He78)27b8b96bde8e36bbbc5e91485b08411a$$aMeyer, Marten$$b2
000170228 7001_ $$aXie, Zhe$$b3
000170228 7001_ $$aGolsaz-Shirazi, Forough$$b4
000170228 7001_ $$aLoffredo-Verde, Eva$$b5
000170228 7001_ $$aFestag, Julia$$b6
000170228 7001_ $$aBockmann, Jan Hendrik$$b7
000170228 7001_ $$aZhao, Lili$$b8
000170228 7001_ $$aStadler, Daniela$$b9
000170228 7001_ $$aChou, Wen-Min$$b10
000170228 7001_ $$aTedjokusumo, Raindy$$b11
000170228 7001_ $$aWettengel, Jochen Martin$$b12
000170228 7001_ $$aKo, Chunkyu$$b13
000170228 7001_ $$aNoeßner, Elfriede$$b14
000170228 7001_ $$0P:(DE-He78)8a8d6fb28cd77106b895bffdaa346dcd$$aBulbuc, Nadja$$b15
000170228 7001_ $$aShokri, Fazel$$b16
000170228 7001_ $$aLüttgau, Sandra$$b17
000170228 7001_ $$0P:(DE-He78)66ed2d4ec9bc11d29b87ac006adf85e5$$aHeikenwälder, Mathias$$b18
000170228 7001_ $$aBohne, Felix$$b19
000170228 7001_ $$0P:(DE-HGF)0$$aMoldenhauer, Gerhard$$b20
000170228 7001_ $$0P:(DE-He78)b2290261145f21c46f2d42783c69d104$$aMomburg, Frank$$b21
000170228 7001_ $$aProtzer, Ulrike$$b22
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