Efficacy of instillation of MB49 cells and thermoreversible polymeric gel in urothelial bladder carcinoma immunization

Abstract

Background Activating the immune system for therapeutic benefit has long been a goal in immunology, especially in cancer treatment, but the low immunogenicity of antitumor vaccines remains a limiting factor in the fight against malignant neoplasms. The increase in the immunogenicity of weak antigens using biodegradable polymers, such as chitosan, has been observed in the field of cancer immunotherapy. However, the effects of the vaccine using a combination of tumor cells and a thermoreversible delivery system based on chitosan in bladder cancer models, mainly using the intravesical route to stimulate the antitumor immune response, are unknown. We propose to evaluate the efficacy of a polymeric gel matrix (TPG) formed by poloxamer 407 and chitosan, associated with MB49 cells, as an intravesical antitumor vaccine using a C57BL/6 murine model of bladder urothelial carcinoma. The effectiveness of immunization was analyzed with the formation of three experimental groups: Control, TPG and TPG + MB49. In the vaccination phase, the TPG + MB49 group underwent a traumatic injury to the bladder wall with immediate intravesical instillation of the vaccine compound containing MB49 cells embedded in TPG. The TPG group was subjected to the same procedures using the compound containing the gel diluted in medium, and the control group using only the medium. After 21 days, the animals were challenged with tumor induction. Results In vitro tests showed loss of viability and inability to proliferate after exposure to TPG. In vivo tests showed that animals previously immunized with TPG + MB49 had higher cumulative survival, as well as significantly lower bladder weight and size in contrast to the other two groups that did not show a statistically different tumor evolution. In addition, the splenocytes of these animals also showed a higher rate of antitumor cytotoxicity in relation to the TPG and control groups. Conclusions We can conclude that MB49 cells embedded in a polymeric thermoreversible gel matrix with chitosan used in the form of an intravesical vaccine are able to stimulate the immune response and affect the development of the bladder tumor in an orthotopic and syngeneic C57BL/6 murine model.

Advances in preclinical approaches for intravesical therapy of bladder cancer

“…Animals immunized with the TPGþMB49 vaccine showed higher cumulative survival rates, significantly reduced bladder weight and size compared to the other groups (Fig. 1) [19]. This revealed that incorporation of MB49 cells into the chitosan-based thermos-reversible polymeric gel matrix and using it as an intravesical vaccine can trigger immune responses and slow the growth of bladder tumors in vivo [19].…”

“…Recent progress in cancer immunotherapy suggests that biodegradable polymers such as chitosan could enhance the effectiveness of weak antigens [19]. The feasibility of this was evidenced by a recent study, which assessed the effectiveness of a polymeric gel matrix (TPG) consisting of poloxamer 407 and chitosan, along with MB49 cells, as an intravesical anticancer vaccination in a C57BL/6 mouse model of bladder urothelial carcinoma [19]. The efficacy of vaccination was evaluated by dividing mice into three groups: control, TPG, and TPGþMB49.…”

“…1) [19]. This revealed that incorporation of MB49 cells into the chitosan-based thermos-reversible polymeric gel matrix and using it as an intravesical vaccine can trigger immune responses and slow the growth of bladder tumors in vivo [19].…”

“…BCG is the established treatment for high-risk NMIBC, but there are limited options for patients who do not respond to BCG [21]. Huang and colleagues investigated the effects of E7766, a macrocyclic-bridged STING agonist, administered directly into the bladder, in two mouse models of NMIBC that were Adapted from [19] with permission from Springer Nature.…”

“…(b) Tumor growth rates calculated by dividing bladder weight by days from induction to euthanasia. (c) Bladders of euthanized animals, categorized by collection day.Adapted from[19] with permission from Springer Nature.…”