Infliximab does not increase colonic cancer risk associated to murine chronic colitis

Abstract

AIMTo explore the influence of Infliximab (IFX) on cancer progression in a murine model of colonic cancer associated to chronic colitis.METHODSAOM/DSS model was induced in C57BL/6 mice. Mice were injected with IFX (5 mg/kg) during each DSS cycle while control mice received saline. Body weight, occult blood test and stool consistency were measured to calculate the disease activity index (DAI). Mice were sacrificed at week 10 and colons were analyzed macroscopically and microscopically for number of cancers and degree of inflammation. MTT assay was performed on CT26 to evaluate the potential IFX role on metabolic activity and proliferation. Cells were incubated with TNF-α or IFX or TNF-α plus IFX, and cell vitality was evaluated after 6, 24 and 48 h. The same setting was used after pre-incubation with TNF-α for 24 h.RESULTSIFX significantly reduced DAI and body weight loss in mice compared with controls, preserving also colon length at sacrifice. Histological score was also reduced in treated mice. At macroscopic analysis, IFX treated mice showed a lower number of tumor lesions compared to controls. This was confirmed at microscopic analysis, although differences were not statistically significant. In vitro, IFX treated CT26 maintained similar proliferation ability at MTT test, both when exposed to IFX alone and when associated to TNF-α.CONCLUSIONIFX did not increase colonic cancer risk in AOM-DSS model of cancer on chronic colitis nor influence directly the proliferation of murine colon cancer epithelial cells.

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

“…Through sequence alignment, we observed a high degree of conservation in the cell factor sequences between human and murine sources. This guided our choice for the dosage of IFX antibody injections in our animal experiments, referencing previous literature on murine models 67 . The antibody was diluted to a 100 µg/mL concentration in PBS and administered via intraperitoneal injections of 500 µL on days 1, 3 and 6 after DSS treatment.…”

“…This guided our choice for the dosage of IFX antibody injections in our animal experiments, referencing previous literature on murine models. 67 The antibody was diluted to a 100 µg/mL concentration in PBS and administered via intraperitoneal injections of 500 µL on days 1, 3 and 6 after DSS treatment. The control group was given the same amount of saline physiological solution via intraperitoneal injection.…”

Infliximab inhibits TNF-α-dependent activation of the NLRP3/IL-1β pathway in acne inversa

“…Three weeks later, murine AI models were performed for blocking antibody experiments. The dosage and injections strategy of IFX in current animal experiments were referenced to previous literatures on murine models [ 16 , 17 ]. The murine AI models received IFX (5 mg/kg) (MCE, NJ, USA) or isotype control (clone HRPN, BioXCell) once a week for two weeks by intraperitoneal injection.…”

Apoptotic cell death in disease—Current understanding of the NCCD 2023

“…Along similar lines, while the ablation of Tnfrsf10b (leading to lack of mTRAIL-R) in mice did not impact tumorigenesis induced by Apc mutations [ 819 ], the administration of TRAIL suppressed tumorigenesis in a mouse model of colitis-associated colon cancer [ 824 ]. Despite some contention in this respect [ 825 – 828 ], TNF seems to contribute to the development of colorectal cancer, although whether such effects depend on the apoptotic function of TNF needs to be formally established. The administration of TNF blockers [ 829 – 833 ] or ablation of Tnf [ 834 ] or Tnfrsf1a [ 834 , 835 ] limits colorectal oncogenesis, as shown in animal models of colorectal cancer induced by colitis, chemicals, or mutations in Apc .…”