Recently, the cases of breakthrough infection and restored virus of COVID-19 have increased after full vaccination, which might be contributed by immune surveillance escape or rebound virus. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides are designed based on the well-conserved S2 region of the COVID-19 spike protein regardless of rapid mutation and glycosylation hindrance. Through HLA molecule presentation, UC peptides can activate cytotoxic T lymphocytes (CTLs), which elicit cytotoxic activity by recognizing COVID-19 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides showed immunogenicity and generated a specific antibody in mice either by intramuscular injection or oral delivery without an adjuvant formulation. In conclusion, the T cell vaccine could provide long-lasting protection against COVID-19 either during reinfection or during the rebound of COVID-19. With the eradication of COVID-19 virus-infected cells, the COVID-19 T cell vaccine might provide a solution to lower COVID-19 severity and long COVID.

Breast cancer is a serious health care issue with millions of women being diagnosed worldwide. Although RAS is mutated in only a minor fraction of breast cancers, the Ras signaling pathway is hyperactivated in half of these tumors. Tamoxifen is most commonly used as hormone therapy for breast cancer, which usually accompanied not serious but bothersome side effects. AP-102 and AP-103 are approved drugs in treating diabetes and antipyretic and analgesic, respectively. Repurposing approved drugs for cancer represents an opportunity to improve advance patients therapies based on the new findings and clinical treatment experience via new proposed signaling pathway. In this study, the antitumor efficacy of two drugs was evaluated on the estrogen-dependent ZR-75-1 human breast cancer xenograft model. The tumor-bearing mice were randomly divided into 5 groups and administrated with vehicle, AP-102, AP-103, AP-102 plus AP-103, and paclitaxel, respectively. Results showed that the tumor inhibition rate of AP-102, AP-103, AP-102/AP-103, and paclitaxel were 27.25%, 17.3%, 43.42%, and 14.25%, respectively. Mechanistic analyses revealed that combination of AP-102 and AP-103 is deduced by inhibiting RAF/ERK activation. Moreover, the mice treated with AP-102/AP-103 showed an increase of 36.5% in white blood cell count compared with the mice treated with vehicle. These data posed an apparent anticancer effect in combination of AP-102 and AP-103 with significant difference, which might be associated with innate immunity evidenced by increased WBC number. For in vitro cytotoxicity, ZR-75-1 cells showed more resistant to paclitaxel than MDA-MB-231 cells. This study provides the important information that combination of two drugs, AP-102 and AP-103, might have potential therapeutic use for tumor cells with highly expressed estrogen receptors or breast tumor resistance to chemo drugs. Citation Format: Pei-Yi Tsai, Yu-Sian Ding, Le-Mei Hung, Yueh-Feng Ho, Ling-Chiu Peng, Chiung-Wen Liou, Jia-Ming Chang. Repurposing of AP-102 and AP-103 in the treatment of breast cancer via inhibiting the RAF/ERK pathway. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr A39. doi: 10.1158/1557-3125.RASONC14-A39

Recently, neuroendocrine tumors (NETs) are increased and mostly occurred in gastrointestinal tract and lung in the worldwide. It secretes functional hormones and non-functional neural transmitters to affect patients unwell so called carcinoid syndrome. In clinically, surgical removal and somatostatin treatment are used to ease the syndrome by NETs. A new strategy for advanced NETs is used by targeting mTOR signaling and neovascularization. In 2011, Everolimus, an mTOR inhibitor, was approved for the treatment of progressive NETs of pancreatic origin in patients with unresectable, locally advanced or metastatic disease, but safety and effectiveness of everolimus have not been established. In this study, low dose of mTOR inhibitor was investigated for capability in modifying the carcinoid syndrome. In an NCI-H727 NET xenograft model, the level of chromogranin A (CgA) was determined in accordance with tumor volume. With multiplexing the serum hormones, alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin were lowered in tumor-bearing mice, but they were rebound when animals treated with Everolimus. Another mTOR inhibitor INK 128 had no apparent tumor inhibition in the same model with doses ranged from 0.25-1 mg/kg. There was no change in the level of CgA in INK128-treated tumor-bearing mice but alpha-MSH level was restored compared with normal mice at a dose-dependent manner. In conclusion, we discovered that low dose of mTOR inhibitor could modify the carcinoid syndrome, where alpha-MSH and beta-endorphin may serve as biomarkers for prognoses of mTOR treatment. Citation Format: I-Hua Liu, Yusian Ding, Chiung-Wen Liou, Jia-Ming Chang. Serine/threonine kinase inhibitors on improving symptoms of neuroendocrine tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 679. doi:10.1158/1538-7445.AM2017-679