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Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas.

Abstract：

:Escape from immune detection favors both tumor survival and progression, and new approaches to circumvent this are essential to combat cancers. Nonvirulent, tumor-tropic bacteria, such as Salmonella typhimurium, can unmask a tumor by transforming it into a site of inflammation; however, the nonspecific invasiveness of Salmonella leads to off-target effects diluting its therapeutic efficacy and making its use in human patients inherently risky. Here, we demonstrate that Salmonella tumor specificity can be significantly improved via a surface-expressed single-domain antibody directed to a tumor-associated antigen (CD20). Antibody-dependent bacterial targeting specifies the infection of CD20+ lymphoma cells in vitro and in vivo, while significantly diminishing nonspecific cell invasion. Indeed, CD20-targeted Salmonella was less generally invasive, even in organs that normally serve as physiological reservoirs. Furthermore, tumor-specific Salmonella engineered to carry the herpes simplex virus thymidine kinase prodrug-converting enzyme effectively treats human lymphoma xenografts when coadministered intratumorally or intravenously with ganciclovir in mice lacking a functional adaptive immune system. Therefore, tumor-targeted Salmonella could prove effective even in those patients displaying a debilitated immune system, which is often the case with late-stage cancers. Altogether, antibody-displaying Salmonella vectors can mediate a tumor-specific response and rejection with few detectable adverse effects while specifically delivering cytotoxic payloads.

journal_name

Blood

journal_title

Blood

authors

Massa PE,Paniccia A,Monegal A,de Marco A,Rescigno M

doi

10.1182/blood-2012-12-474098

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

705-14

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2012-12-474098

journal_volume

122

pub_type

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