Single-step nanoparticle antigen presentation system for tumor immunotherapy

• Published in: Journal for immunotherapy of cancer 2015-11, Vol.3 (Suppl 2), p.P319-P319
• Main Authors: Kohlhapp, Frederick, Huelsmann, Erica, Rudra, Jai, Nabatiyan, Arman, Zloza, Andrew
• Format: Article
• Language: English
• Subjects: Antigens; Breast cancer; Cancer; Care and treatment; Health aspects; Immunotherapy; Innovations; Melanoma; Nanoparticles; Poster Presentation; Tumors
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/2051-1426-3-S2-P319

Background and aimWhile only 10-30% of patients treated with currently approved single immunotherapies demonstrate long-term benefit, treatment efficacy in responders correlates with increased CD8+ T cell responses to neoantigens (tumor antigens hidden from the immune system). Thus, to improve presentation of tumor antigens and expose neoantigens we engineered a single-step nanoparticle antigen presentation system (SNAPS) that enables both membrane and cytosolic cancer proteins to be covalently coupled to an injectable nanoparticle emulsion.MethodsB16 melanoma (SNAPS-B16), primary melanocyte (SNAPS-MEL), 4T1 breast cancer (SNAPS-4T1) lysate or mouse IgG (SNAPS-C) were used for coating polystyrene nanoparticles via an EDAC linker. One day or 11 days post B16-F10 tumor cell challenge (100,000 cells, intradermal, right flank), mice were treated (at the same site as the tumor cell injection) with 200 μL of 1% w/v cell lysate coated nanoparticles. Tumors were measured using calipers every 2-3 days. Flow cytometry staining was performed for antigen presenting cells (APCs) and CD8+ T cells after dissection and mechanical dissociation of the tumor. Statistical analyses were performed using the student t test and Prism v4.0 software (GraphPad). Differences with a P < 0.05 were considered statistically significant.ResultsWe observed that SNAPS-B16 delivered at one day post tumor challenge significantly reduced tumor growth (P < 0.01) compared to SNAPS-C (which had no effect). SNAPS delivered at day 11 (when tumors were approximately 5 mm × 5 mm) significantly halted tumor growth (< 2-fold increase over the course of 10 days) while B16 treated with SNAPS-C increased ~16-fold (P < 0.01). Neither SNAPS-4T1 nor SNAPS-MEL had any effect on the growth of B16 in vivo, demonstrating the induction of an antigen-specific anti-tumor response with SNAPS-B16. Additionally, SNAPS-B16 significantly increased (P < 0.01) the proportion of APCs within the tumor microenvironment compared to the SNAPS-C, as evidenced by the increased percentage of MHC-II+ cells).ConclusionsOur results demonstrate that SNAPS coupling of whole tumor lysate from cancer cells to nanoparticles delivers a robust anti-tumor immune response resulting in enhanced tumor regression. These findings demonstrate that a cancer-derived protein unique to B16 melanoma (rather than to tumors in general or to normal melanocytes) coating the SNAPS confers tumor specificity. Although preliminary, our reported innovation of