Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk. The immunogenicity of the neoantigen was profoundly potentiated by efficient codelivery of neoantigen and dual synergistic adjuvants, which is accompanied by reduced acute systemic toxicity. BanNVs sensitized immune checkpoint programmed death receptor 1 (PD-1) on T cells, therefore, a combination of banNVs with aPD-1 conspicuously induced the therapy response and led to complete regression of 70% neoantigenspecific tumors without recurrence. We conclude that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy. A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer. Sci. Adv. 6, eaaw6071 (2020).

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A comparative study investigating the integration of supplemental teaching resources in materials science education was developed for the purpose of determining the effectiveness of teaching strategies. Digital stories created by students, excerpts from the Nova Making Stuff documentaries, YouTube educational videos and student generated demo-kits were used as part of the investigation whereby two 9th grade science classes (n~26) were evaluated. Each participant in the study received one period (40-min) of a traditional lesson on Materials Science including specific content, vocabulary, and a pre- and post- lesson assessment. Additionally, the students in each class participated in a 30-min supplemental component, e.g. video or activity-based demonstration using aforementioned kits or video compilation. Pre- and post- evaluations (e.g. open-ended and likert questions) were administered to all of the participants. As hypothesized, the students’ feedback and performance on assessment activities reveal that the use of multimedia and activity-based resources may be equally effective teaching methods as traditional methods.

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Objectives. Veliparib (ABT), a PARP1/2 inhibitor, has been studied in ovarian adenocarcinoma treatment, particularly in conjunction with platinum therapy, and sensitizes cells to cisplatin (Cis). Pifithrin-α (PFT), a transcriptional inhibitor of p53, sensitizes p53 wild-type ovarian cancer cells to antimicrotubule agent-induced apoptosis. No studies have evaluated the interaction of PFT with platinum drugs or PARP inhibitors. We evaluated the potential synergistic interactions between PFT and ABT/Cis in p53 intact ovarian cancer cells. Methods. We conducted clonogenic assays using BG-1, a human ovarian adenocarcinoma cell line with WT p53 activity. Cells were seeded in 6-well plates and, after 24 hours, treated with combinations of 5μM PFT and multiple doses of ABT and Cis. After 8 days, colony counts were obtained with automated GelDoc software. To identify synergistic interactions, Combination Indices (CI) were calculated with Calcusyn software. Results. At the lowest dose of Cis (0.625μM), relative cell survival is 60.4% with Cis-PFT, 64.9% with Cis-ABT, and 24.5% with Cis-ABT-PFT. At the highest dose (10μM), relative cell survival is 34.3% with Cis-PFT, 5.25% with Cis-ABT, and 0.85% with Cis-ABT-PFT. At low concentrations of Cis, Cis-PFT showed mild to moderate antagonism. At Cis concentrations >2.5μM, moderate synergism developed. At all concentrations, PFT-ABT showed moderate to strong antagonism. Cis-ABT-PFT showed moderate to strong synergism at all concentrations. Conclusions. PFT sensitizes BG-1 cells to Cis in a dose dependent pattern, improving synergism at increasing doses of both Cis and PFT. In contrast, PFT shows marked antagonism to the cytotoxic effects of ABT, independent of ABT dose. The combination of ABT+PFT shows strong, dose-independent synergism in the sensitization of BG-1 cells to Cis and significantly reduces relative survival, suggesting the potential for improved tumor control at reduced doses of cisplatin in p53 WT ovarian cancer. Pifithrin-α and veliparib synergize in the sensitization of BG-1 cells to cisplatin therapy Cis (μM) ABT (μM) PFT (μM) CI Synergy Cisplatin + Pifithrin-α 0.625 − 5 1.729 −−− 1.25 − 5 1.342 −− 2.5 − 5 0.865 + 5 − 5 0.469 +++ 10 − 5 0.390 +++ Veliparib + Pifithrin-α − 0.625 5 1.803 −−− − 1.25 5 3.325 −−−− − 2.5 5 1.647 −−− − 5 5 2.657 −−− − 10 5 1.503 −−− Cisplatin + Veliparib 0.625 1.25 − 0.566 +++ 1.25 2.5 − 0.794 ++ 2.5 5 − 0.863 + 5 10 − 0.656 +++ 10 20 − 0.823 ++ Cisplatin + Veliparib + Pifithrin-α 0.625 1.25 5 0.293 ++++ 1.25 2.5 5 0.418 +++ 2.5 5 5 0.392 +++ 5 10 5 0.291 ++++ 10 20 5 0.262 ++++ Synergism: CI<1, “+” Antagonism: CI>1, “−” Citation Format: Margaret Whicker, Brian Liang, Z. Ping Lin, Alan Sartorelli, Elena Ratner. Pifithrin-α and veliparib synergize in the sensitization of p53 wild-type ovarian cells to cisplatin therapy. [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 3277. doi:10.1158/1538-7445.AM2013-3277