Identification and validation of HLA-A24 XBP1, CD138, and CS1 peptides and induction of antigensspecific CD8+ T cell immunity using a multipeptide cocktail: Preclinical basis for vaccine therapy in HLA-A24 patients with

Global Summit on Oncology & Cancer

May 25-27, 2017 Osaka, Japan

Jooeun Bae, Derin Keskin, Jun Zhou, Guanglan Zhang, Dharminder Chauhan, Teru Hideshima, Noopur Raje, Paul Richardson, Nikhil Munshi and Kenneth C Anderson

Dana-Farber Cancer Institute, USA
Harvard Medical School, USA
Boston University, USA
Massachusetts General Hospital, USA
VA Boston Healthcare System, USA

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

XBP1 (X-box binding protein 1), CD138 (Syndecan-1) and CS1 (SLAMF7) are highly expressed antigens associated with tumor pathogenesis in cancers including multiple myeloma (MM) and various solid tumors. We have previously reported on the use of HLA-A2 peptides specific to these antigens to generate specific cytotoxic T cells (CTL). Vaccinations with these pooled peptides are currently in phase I/II clinical trials in patients with smoldering MM or triple negative breast cancer. The current studies extend this concept to the patients with HLA-A24, the second most dominant MHC-Class I in North America and the most common in Asia to broaden the patient population eligible for this cancer vaccine. Immunogenic HLA-A24 peptides derived from the antigens were evaluated. The identified XBP1 unspliced (UN)185-193 (I S P W I L A V L), XBP1 spliced (SP)223-231 (V Y P E G P S S L), CD138265-273 (I F A V C L V G F) and CS1240-248 (L F V L G L F L W) peptides were highly HLA-A24-specific and immunogenic, and induced ex vivo antigen-specific CTL with anti-MM activity in an HLA-A24 specific manner. Furthermore, a cocktail containing the four HLA-A24 peptides evoked MM-specific CTL with distinct phenotypic profiles (CD28, CD40L, 41BB, CD38, CD69) and antitumor activities, evidenced by perforin/CD107a/IFN-�³/IL-2/TNF-�± production induced by HLA-A24+ MM cells. The multipeptidespecific CTL included antigen-specific memory CD8+ T cell subsets expressing T cell activation and immune checkpoints antigens (CTLA, PD1, LAG3, TIM3). Treatment of the multipeptide-CTL with specific inhibitors against mTOR, AKT, HDAC6 or specific immune checkpoints enhanced frequency/activation of antigen-specific central memory CTL and their anti-tumor activity. These results highlight the potential therapeutic application of an HLA-A24 multipeptide vaccine to induce MM-specific CTL with a broad spectrum of anti-tumor activity, which may extend to solid tumors (breast, colon, and pancreatic cancer) expressing these antigens.

Biography :

Jooeun Bae has completed his PhD in Biomedical Science from Virginia Polytechnic Institute and State University, Blacksburg, Virginia. He holds a Master’s Degree in Major in Immunology and Microbiology from University of Maryland, Baltimore, Maryland followed by a Bachelor’s Degree from University of Maryland, Baltimore, Maryland. He attended the American Society for Hematology conference in San Diego, California USA.

Email: jooeun_bae@dfci.harvard.edu