Abstract 2889: Human antibodies induced by vaccination with a carbohydrate mimetic-peptide vaccine show functional anti-tumor activity on human lung-cancer cells

Abstract

Abstract Introduction: Lung cancer is the most common cancer worldwide, and the leading cancer killer in both men and women in the United States. The 5-year survival rate for lung cancer ranges from <2% to about 70% depending on stage. Current treatment options including surgery, chemotherapy, and radiotherapy have limited efficacy, as over half of people with lung cancer die within a year of initial diagnosis. Tumor vaccines hold the potential to deliver durable, specific and systemic anti-tumor responses in lung-cancer patients diagnosed with advanced disease. Appearance of tumor-associated carbohydrate antigens (TACAs) is the hallmark of cancer initiation and metastasis in many cancer types, including lung cancer. We have developed active vaccination strategies that target TACAs using peptide mimetics, and successfully vaccinated stage IV breast-cancer patients. The purpose of the current study is to evaluate functionality of vaccine-induced antibodies against lung-cancer cells. Procedure: Patients with stage IV breast cancer underwent vaccination with the carbohydrate mimicking peptide P10s synthesized with the Pan T-cell peptide PADRE (P10s-PADRE). Doses of P10s-PADRE admixed with MONTANIDE™ ISA 51 VG were administered to subjects subcutaneously in rotating injection sites in the abdomen on weeks 1, 2, 3, 7 and 9. Pre-immune (week 1) and post-immune sera (weeks 4 and 7) were tested for functional activity against a non-Small Cell lung-cancer cell line (NCI-H522) and a Small Cell lung-cancer cell line (NCI-H69). Cell-surface carbohydrates were profiled and serum binding to cells was assayed by flow cytometry. Cytotoxicity, migration and invasion assays were performed to assess functional anti-lung cancer-cell activity of the sera. Results: Both cell lines express relevant TACAs that can be targeted with P10s-PADRE immunization. Vaccinated serum reacted with tumor cells, induced toxicity, and prevented tumor-cell migration and invasion in vitro. Conclusion: Our results show that P10s-PADRE vaccination of breast-cancer patients induces functional immune activity against lung-cancer cells. Accordingly, we propose to extend our successful vaccination strategy to lung-cancer patients with advanced stage III/IV disease. This group of patients has poor survival, and induction of functional antibodies can significantly increase disease control and survival rate. Citation Format: Konstantinos Arnaoutakis, Fariba Jousheghany, Issam Makhoul, Laura Hutchins, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Human antibodies induced by vaccination with a carbohydrate mimetic-peptide vaccine show functional anti-tumor activity on human lung-cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2889. doi:10.1158/1538-7445.AM2014-2889