Abstract B041: An injectable magnetic nanogel system for filling surgical residual cavity with effective cancer immunotherapy combined hyperthermic capability

Abstract

Abstract The advancement in nanotechnology has created a wealth of new possibilities for treating cancer with multifunctional nanosystem holding various therapeutic strategies in a single platform. It has been reported that magnetic nanoparticle hyperthermia can induce antitumor immunity whereas the immunotherapy can naturally trigger the immune system with the help of an appropriate stimulator to control cancer. Therefore the present study investigates the effectiveness of a hybrid nanocomposite system to effectively exterminating the tumor associated immune cells (TICs) as well as inducing an inflammatory immune response by activating killer T-cells by combining magnetic hyperthermia with an immunostimulatory agent. Here we report an injectable magnetic nanogels conjugating a checkpoint inhibitor (T-lymphocyte antigen-4 [CTLA4]) and a Toll-like receptor (TLR) agonists (imiquimod) for generating an effective antitumoral immune response for postsurgical glioma treatment. The injectable conductive magnetic hydrogel system enables the tracing and deterring of the recurrent tumor cells via magnetic nanoparticle-mediated hyperthermia with the strong immunologic memory effect. The superparamagnetic iron oxide nanoparticles encapsulated nanogels exhibit an induced heating ability in an alternating magnetic field (AMF) and thereby trigger the tumor cells to undergo a burst release of heat shock proteins to recruit immune cells to generate tumor-allied antigens. These antigens along with the released imiquimod from the hydrogel can generate vaccine-like functionalities. Moreover, the introduction of anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) as a checkpoint-blockade will generate memory T-cells, which in turn will attack the metastatic and recurrent tumor cells. Above all, the conductive bioactive scaffold will support the neuronal regeneration and reactivation of brain cells. Thus our multifunctional novel hydrogel system will be able to fill the surgical residual cavity to prevent the glioma recurrence and will improve the local neuronal tissue reconstruction along with hyperthermic-immunotherapy. Citation Format: Arathyram Ramachandra Kururp Sasikala, Afeesh Rajan Unnithan, Chan Hee Park, Cheol Sang Kim. An injectable magnetic nanogel system for filling surgical residual cavity with effective cancer immunotherapy combined hyperthermic capability [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B041.