Vaccination of High-Risk Breast Cancer Patients with Carbohydrate Mimicking Peptides

摘要

The expression of the Tumor Associated Carbohydrate Antigens such as the neolactoseries antigen Lewis Y (LeY) and gangliosides such as GM2 and GD2/GD3 are amplified on breast cancer cells and is linked to poor prognosis and high risk of disease relapse. Immunotherapy to direct responses to TACA is, therefore, perceived to be of clinical benefit. To overcome this deficiency, we developed mimotopes of TACA to induce more robust cross-reactive and tumor- specific responses. In preclinical studies, immunization with these mimotopes reduce tumor burden and inhibited metastatic outgrowth of murine tumor cells expressing TACA structural homologues. Thus, peptide mimotopes of TACA represent a new and very promising tool to induce a strong immune response to TACA expressed on Breast Cancer cells. Based on encouraging preclinical results, our objectives are for the current funding period (years 1 and 2) are to develop the necessary preclinical data required by the Food and Drug Administration (FDA) for filing an Investigational New Drug (IND). In this context we: (1) Developed the necessary procedures for the required Good Laboratory Practice (GLP) studies; (2) Defined problems in scale up of the manufactured mimotope vaccines; (3) Identified alternative mimotopes of TACA that circumvent the scale up problems.