Targeting Human-Cytomegalovirus-Infected Cells by Redirecting T Cells Using an Anti-CD3/Anti-Glycoprotein B Bispecific Antibody
The host immune response to human cytomegalovirus (HCMV) is effective against HCMV reactivation from latency, though not sufficient to clear the virus. T cells are primarily responsible for the control of viral reactivation. When the host immune system is compromised, as in transplant recipients wit...
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Published in | Antimicrobial agents and chemotherapy Vol. 62; no. 1 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
01.01.2018
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Subjects | |
Online Access | Get full text |
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Summary: | The host immune response to human cytomegalovirus (HCMV) is effective against HCMV reactivation from latency, though not sufficient to clear the virus. T cells are primarily responsible for the control of viral reactivation. When the host immune system is compromised, as in transplant recipients with immunosuppression, HCMV reactivation and progressive infection can cause serious morbidity and mortality. Adoptive T cell therapy is effective for the control of HCMV infection in transplant recipients. However, it is a highly personalized therapeutic regimen and is difficult to implement in routine clinical practice. In this study, we explored a bispecific-antibody strategy to direct non-HCMV-specific T cells to recognize and exert effector functions against HCMV-infected cells. Using a knobs-into-holes strategy, we constructed a bispecific antibody in which one arm is specific for CD3 and can trigger T cell activation, while the other arm, specific for HCMV glycoprotein B (gB), recognizes and marks HCMV-infected cells based on the expression of viral gB on their surfaces. We showed that this bispecific antibody was able to redirect T cells with specificity for HCMV-infected cells
In the presence of HCMV infection, the engineered antibody was able to activate T cells with no HCMV specificity for cytokine production, proliferation, and the expression of phenotype markers unique to T cell activation. These results suggested the potential of engineered bispecific antibodies, such as the construct described here, as prophylactic or therapeutic agents against HCMV reactivation and infection. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Weixu Meng, Division of Hematopoietic Stem Cell and Leukemia Research, Gehr Family Center for Leukemia Research, City of Hope, Duarte, California, USA. Citation Meng W, Tang A, Ye X, Gui X, Li L, Fan X, Schultz RD, Freed DC, Ha S, Wang D, Zhang N, Fu T-M, An Z. 2018. Targeting human-cytomegalovirus-infected cells by redirecting T cells using an anti-CD3/anti-glycoprotein B bispecific antibody. Antimicrob Agents Chemother 62:e01719-17. https://doi.org/10.1128/AAC.01719-17. |
ISSN: | 0066-4804 1098-6596 |
DOI: | 10.1128/AAC.01719-17 |