Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity.
J Biomed Sci
; 29(1): 57, 2022 Aug 12.
Article
in En
| MEDLINE
| ID: mdl-35962391
ABSTRACT
BACKGROUND:
For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma.METHODS:
Female BALB/c mice were implanted subcutaneously with CT26 tumors, a model of colon carcinoma. Mice bearing tumors were selected and administered Albumin-IL-2 (Alb-IL2), a fusion protein, for further analysis of anticancer effect.RESULTS:
We demonstrated that Salmonella SL7207, a genetically modified strain of Salmonella enterica serovar Typhimurium, preferentially accumulates in the tumor microenvironment, potentiating it to stimulate localized innate immunity. We delivered IL-2 as a fusion protein, Alb-IL2, which we demonstrate to have preferential accumulation properties, bringing it to the tumor and secondary lymphoid organs. Treatment of tumor-bearing mice with Salmonella + Alb-IL2 leads to superior tumor control and enhanced overall survival compared to controls. When assessing immunological factors contributing to our observed tumor control, significantly enhanced T cell population with superior effector function was observed in mice treated with Salmonella + Alb-IL2. We confirmed that these T cells were indispensable to the observed tumor control through antibody-mediated T cell depletion experiments.CONCLUSIONS:
These findings highlight the ability of Salmonella + Alb-IL2 to serve as a novel therapeutic approach to induce T cell-mediated antitumor immunity and exert long-term tumor control in a murine model of cancer.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma
/
Colonic Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Biomed Sci
Journal subject:
MEDICINA
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos