Abstract 1270: Mimicking infection for immunotherapy against breast cancer - fooling the immune system.
Authors: Kokate Rutika , Thamake Sanjay , Jones Harlan , Vishwanatha Jamboor , Mott Brittany 
Published: August 2014

Short description: Immunotherapy represents a potential and innovative means to combat cancer. It essentially harnesses the body's immune system to fight against cancer. Previous literature suggests that cancer vaccines designed against a specific tumor antigen have been efficiently utilized to trigger immune responses against tumor cells. Despite the preliminary evidence in animal models, low immunogenicity is one of the major hurdles in the development of vaccines in humans. In order to surmount this obstacle, several approaches including the use of an “ideal” tumor antigen, appropriate delivery techniques, immune boosting strategies with co-stimulatory molecules are being explored.

Purpose: The purpose of this study was to develop “bacteriomimetic nanoparticles” to enhance adaptive cell-mediated immune responses (CD4+ and CD8+ T cell responses) against tumor antigen as a therapeutic option for cancer treatment.

Materials and Methods: NPs were prepared by modified solid/oil/water solvent evaporation method using an ultrasonic processor UP200H system (Hielscher Ultrasonics GmbH, Germany). We used membrane preparations of the 4T1 mouse mammary cancer cell line as a tumor antigen and CpG ODN's as a “bactriomimetic” stimulant. Fourteen days before tumor challenge BALB/c female mice (6-8 weeks) were pre-immunized with CpG followed by secondary immunization using respective NPs encapsulated with the membrane antigen preparation. Subsequently, mice (n=4) were challenged with 105 tumor cells intravenously (IV). Mice were sacrificed and tumors were harvested at days 3, 7 and 14 respectively. CD4+ and CD8+ T cell responses were measured in lower respiratory node and spleen using flow cytometry. In another experimental set, following the same immunization schedule as mentioned above, mice (n=5) were challenged subcutaneously (SC) with 105 tumor cells. Primary tumor size was monitored using vernier caliper and bioluminiscence imaging (Caliper Life Sciences Inc., MA, USA). Mice were sacrificed on day sixteen after tumor challenge; spleen cells were used for flow cytometric analysis and primary tumor tissue was used to evaluate CD4+ and CD8+ T cell via immunohistochemistry.

Results: We found significant reduction in progression of tumor growth in mice immunized with CpG coated NPs containing tumor antigen (CpG-NP-Tag). Cytometry analysis demonstrated increased CD4+ (helper) and CD8+ (cytotoxic) T cell response emphasizing enhanced immunogenicity against cancer cells. IHC data indicated greater CD4+ T cell infiltration of the tumor tissue for the animals immunized with CpG-NP-Tag.

Conclusions: Primary tumor size, IHC and flow cytometry analysis indicate that CpG-NP-Tag NPs were successfully employed to boost the immune response against tumor cells.

Citation Format: Rutika Kokate, Sanjay Thamake, Harlan Jones, Jamboor Vishwanatha, Brittany Mott. Mimicking infection for immunotherapy against breast cancer - fooling the immune system. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1270. doi:10.1158/1538-7445.AM2013-1270