Interleukin-17A (IL-17A) is a pro-inflammatory cytokine produced by T H 17 cells that participate in and contribute to host defense and autoimmune diseases. We recently reported the antitumor properties of the probiotic strain Lactobacillus casei BL23 and TH17 cells in mice was shown to play an important role in this beneficial effect.
In order to better understand the role of IL-17A in cancer, we construct strain recombinant of Lactococcus lactis produce this cytokine and we are determined biological activity in: (i) the test bioassay for the induction of IL-6 production of fibroblasts murine 3T3 L1 cell line and (ii) The allograft mouse models of human papilloma virus (HPV) induced cancer.
Our data indicate that the recombinant L. lactis produce and efficiently secrete biologically active IL-17A cytokine. Interestingly, ~ 26% of mice treated with L. lactis intranasal-IL-17A and challenged with TC-1 cells remained tumor free through an experiment, in contrast to the control mice treated with wild strains of L. lactis developed 100% tumor is aggressive.
In addition, the median size of ~ 74% tumor-bearing mice treated with recombinant L. lactis-IL-17A, significantly lower than mice treated with L. lactis-wt. Overall, our results indicate that the intranasal administration of L. lactis secreting IL-17A results in partial protection against TC-1 tumor-induced in rats, confirming the antitumor effects of this cytokine is in our cancer model.
Anti-colorectal cancer effects of anti-p21Ras scFv delivered by the recombinant adenovirus KGHV500 and cytokine-induced killer cells.
Colorectal cancer (CRC) is the most common type of gastrointestinal cancer. CRC adenovirus-mediated gene therapy holds great promise for the treatment of malignancies. However, the intravenous delivery of adenovirus limited exhibit anti-tumor activity in vivo when used alone.
In this study, the antitumor activity of recombinant adenovirus KGHV500 assessed by MTT, TUNEL, Matrigel invasion and cell migration test. To improve the intravenous delivery KGHV500 vivo cytokine-induced killer (CIK) cells are used as vectors to carry KGHV500 second. We explored whether CIK cells can carry KGHV500 recombinant adenovirus containing anti-p21Ras single chain variable antibody fragment (scFv) gene into the tumor and increase the antitumor potential.
Our results indicate that KGHV500 showed significant antitumor activity in vitro. In mouse xenograft tumor model SW480 nude, combined with KGHV500 CIK cells can induce a higher antitumor activity against colorectal cancer in vivo than that caused by either CIK or KGHV500 only. After seven days of treatment, adenovirus and scFv was detected in tumor tissue but not in normal tissues was detected by immunohistochemistry. Therefore, KGHV500 replicates in tumor and anti-p21Ras managed to express scFv in a xenograft model of colorectal cancer.
Our study provides a new strategy for the treatment of colorectal cancer by combining the CIK cells with recombinant adenovirus KGHV500 conducted scFv anti-p21 Ras.