Local application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620987
Title:
Local application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection.
Authors:
Kocijancic, Dino; Felgner, Sebastian; Schauer, Tim; Frahm, Michael; Heise, Ulrike; Zimmermann, Kurt; Erhardt, Marc ( 0000-0001-6292-619X ) ; Weiss, Siegfried
Abstract:
Cancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8+ T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Local application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection. 2017 Oncotarget
Journal:
Oncotarget
Issue Date:
7-Jun-2017
URI:
http://hdl.handle.net/10033/620987
DOI:
10.18632/oncotarget.18392
PubMed ID:
28637010
Type:
Article
Language:
en
ISSN:
1949-2553
Appears in Collections:
publications of the research group molecular Immunology (MOLI); publications of the department of molecular Infectionbiology (MIBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKocijancic, Dinoen
dc.contributor.authorFelgner, Sebastianen
dc.contributor.authorSchauer, Timen
dc.contributor.authorFrahm, Michaelen
dc.contributor.authorHeise, Ulrikeen
dc.contributor.authorZimmermann, Kurten
dc.contributor.authorErhardt, Marcen
dc.contributor.authorWeiss, Siegfrieden
dc.date.accessioned2017-07-04T13:27:49Z-
dc.date.available2017-07-04T13:27:49Z-
dc.date.issued2017-06-07-
dc.identifier.citationLocal application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection. 2017 Oncotargeten
dc.identifier.issn1949-2553-
dc.identifier.pmid28637010-
dc.identifier.doi10.18632/oncotarget.18392-
dc.identifier.urihttp://hdl.handle.net/10033/620987-
dc.description.abstractCancer is a devastating disease and a large socio-economic burden. Novel therapeutic solutions are on the rise, although a cure remains elusive. Application of microorganisms represents an ancient therapeutic strategy, lately revoked and refined via simultaneous attenuation and amelioration of pathogenic properties. Salmonella Typhimurium has prevailed in preclinical development. Yet, using virulent strains for systemic treatment might cause severe side effects. In the present study, we highlight a modified strain based on Salmonella Typhimurium UK-1 expressing hexa-acylated Lipid A. We corroborate improved anti-tumor properties of this strain and investigate to which extent an intra-tumoral (i.t.) route of infection could help improve safety and retain advantages of systemic intravenous (i.v.) application. Our results show that i.t. infection exhibits therapeutic efficacy against CT26 and F1.A11 tumors similar to a systemic route of inoculation. Moreover, i.t. application allows extensive dose titration without compromising tumor colonization. Adverse colonization of healthy organs was generally reduced via i.t. infection and accompanied by less body weight loss of the murine host. Despite local application, adjuvanticity remained, and a CT26-specific CD8+ T cell response was effectively stimulated. Most interestingly, also secondary tumors could be targeted with this strategy, thereby extending the unique tumor targeting ability of Salmonella. The i.t. route of inoculation may reap the benefits of systemic infection and aid in safety assurance while directing potency of an oncolytic vector to where it is most needed, namely the primary tumor.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleLocal application of bacteria improves safety of Salmonella-mediated tumor therapy and retains advantages of systemic infection.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalOncotargeten
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