Targeting cytomegalovirus-infected cells using T cells armed with anti-CD3 × anti-CMV bispecific antibody.
Biol Blood Marrow Transplant
; 18(7): 1012-22, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22313635
ABSTRACT
Human cytomegalovirus (CMV) reactivation and infection can lead to poor outcomes after allogeneic stem cell transplantation. We hypothesized that anti-CD3 activated T cells (ATCs) armed with chemically heteroconjugated anti-CD3 × polyclonal anti-CMV bispecific antibody (CMVBi) will target and eliminate CMV-infected cells. Arming doses of CMVBi as low as 0.01 ng/10(6) ATCs was able to mediate specific cytotoxicity (SC) directed at CMV-infected target cells significant above unarmed ATCs at mutiplicities of infection (MOI) between 0.01 and 1. At effector-to-target ratios (ET) of 251, 12.51, 6.251, and 3.1251, armed ATCs significantly enhanced killing of CMV-infected targets compared with unarmed ATCs. At an MOI of 1.0, the mean % SC directed at CMV-infected targets cells for CMVBi-armed ATCs at ET of 3.12, 6.25, and 12.5 were 79%, 81%, and 82%, respectively; whereas the mean % SC for unarmed ATCs at the same ET were all <20%. ATCs, Cytogam(®), or CMVBi alone did not lyse uninfected or CMV-infected targets. Co-cultures of CMVBi-armed ATCs with CMV-infected targets induced cytokine and chemokine release from armed ATCs. This nonmajor histocompatibility complex restricted strategy for targeting CMV could be used to prevent or treat CMV infections after allogeneic stem cell transplantation or organ transplantation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Complexo CD3
/
Anticorpos Biespecíficos
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Citomegalovirus
/
Anticorpos Antivirais
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article