Abstract 2533: A novel approach to generate anti-Tn antibody for cancer diagnosis and immunotherapy

Abstract

Abstract Alterations in carbohydrate epitopes present on the cell surface are often hallmark of the transition from normal to neoplastic tissue. The concept of using carbohydrate antigens as cancer marker has thus spurred intense research interests into exploiting TACAs for the development of anticancer vaccines. This study presents a novel carrier protein containing a binding domain to the receptor of antigen presenting cells (APC) and cysteine-rich repeat peptide to serve as docking sites for conjugating tumor associated carbohydrate antigens (TACAs) or haptens. This novel carrier protein after conjugation with Tn, (GalNAcα1-O-Ser/Thr), can effectively elicit high titer of IgG1 antibody rather than IgM against Tn with high specificity in immunized mice. We then performed immunohistochemical (IHC) staining of twenty-six prostate cancer samples by staining with anti-Tn antibody, and we observed that the IHC staining with anti-Tn antibody is proportional to the malignancy of prostate cancer. Furthermore, we have examined the anti-Tn vaccine potency in Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice. TRMAP mice, which were treated with anti-Tn vaccine, showed longer survival rate and delayed tumor growth. We also successfully constructed the cDNA of mouse anti-Tn antibody from hybridoma cell line, and engineer this mouse cDNA as single-chain anti-Tn mouse antibody and anti-Tn immunotoxin. Our preliminary results showed that anti-Tn single-chain antibody can as a diagnostic antibody to distinguish normal prostatic tissue and prostate cancer, and anti-Tn immunotoxin can inhibit tumor cell growth. This study presents that our carrier protein can offer a platform for designing vaccine against tumor-associated weak immunogen and applies a new strategy in cancer immunotherapy in future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2533. doi:1538-7445.AM2012-2533