Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas
Articolo
Data di Pubblicazione:
2013
Citazione:
Salmonella engineered to express CD20-targeting antibodies and a drug-converting enzyme can eradicate human lymphomas / P.E. Massa, A. Paniccia, A. Monegal, A. de Marco, M. Rescigno. - In: BLOOD. - ISSN 0006-4971. - 122:5(2013), pp. 705-714.
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Antibodies, Monoclonal; Antigens, CD20; Cell Line, Tumor; Female; Gene Expression; Genetic Engineering; Humans; Lymphoma; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Prodrugs; Recombinant Proteins; Remission Induction; Salmonella typhimurium; Thymidine Kinase; Xenograft Model Antitumor Assays; Hematology; Biochemistry; Cell Biology; Immunology
Elenco autori:
P.E. Massa, A. Paniccia, A. Monegal, A. de Marco, M. Rescigno
Link alla scheda completa: