Abstract 5634: Chemical antibodies for cancer immunotherapy

The absence of curative therapies for recurrent forms of metastatic cancer has prompted a vigorous search for novel treatment strategies. Cancer immunotherapy uses the host immune system, either directly or indirectly, to combat cancer. The more successful cancer immunotherapies are antibody-based. In this study we hypothesized that a chemical antibody (chembody) with an intact Fc region can be constructed by conjugating tumor cell specific peptidomimetic agents (ligands) to the Fab region of human IgG (hIgG). The ligand of interest, RGD, binds effectively to αVβ3 integrin expressed on tumor cells. The resultant chembody will have the ability to opsonize the tumor cells and elicit host immune response against cancer cells by recruiting the immune effector cells. In this study, we (1) conjugate naïve hIgG with the ligand, (2) verify ligand conjugation, and (3) test the efficacy of the chembody. The 2-iminothiolane conjugation method was employed to conjugate the ligand to naïve hIgG. The conjugation was verified by performing Western blot analysis, MALDI-MS assay, and cell binding assay. The Western blot and Coomassie blue staining showed that conjugation was successful while the MALDI-MS assay showed a 1:3 conjugation ratio. Colorimetric cytotoxicity assay will be used to test the efficacy of the chembody. We expect chembodies with intact Fc region to be tumor specific, and actively recruit immune cells to the tumor site and have low immunogenicity. This novel individualized medicine approach in cancer immunotherapy can be very effective in eliminating the remaining cells responsible for relapse after chemotherapy or radiotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5634.