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

Paul E. Massa, Aida Paniccia, Ana Monegal, Ario De Marco, Maria Rescigno

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Escape from immune detection favors both tumor survival and progression, and new approaches to circumvent this are essential to combat cancers. Nonvirulent, tumortropic 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.

Original languageEnglish
Pages (from-to)705-714
Number of pages10
JournalBlood
Volume122
Issue number5
DOIs
Publication statusPublished - Aug 1 2013

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Salmonella
Tumors
Lymphoma
Antibodies
Enzymes
Pharmaceutical Preparations
Neoplasms
Immune system
CD20 Antigens
Single-Domain Antibodies
Immune System
Bacterial Antibodies
Ganciclovir
Thymidine Kinase
Prodrugs
Viruses
Heterografts
Neoplasm Antigens
Simplexvirus
Salmonella typhimurium

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas. / Massa, Paul E.; Paniccia, Aida; Monegal, Ana; De Marco, Ario; Rescigno, Maria.

In: Blood, Vol. 122, No. 5, 01.08.2013, p. 705-714.

Research output: Contribution to journalArticle

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