Preparation of autologous leukemia and lymphoma vaccines expressing alpha-Gal epitopes

This study describes a novel method for increasing the immunogenicity of au tologous tumor vaccines in leukemia and lymphoma patients by exploiting the natural anti-Gal antibody for in situ targeting of the vaccinating cells t o antigen-presenting cells (APCs). Incubation of leukemia or lymphoma cells with neuraminidase and recombinant alpha1,3-galactosyltransferase results in the synthesis of many alpha -gal epitopes (Gal alpha1-3Gal beta1-4GlcNAc -R) on their cell membranes. Vaccination with such processed tumor cells re sults in the binding of the natural anti-Gal immunoglobulin G (IgG) antibod y to these epitopes and opsonization of these cells for effective phagocyto sis by APCs, such as dendritic cells and macrophages. These APCs may transp ort the vaccine to adjacent draining lymph nodes for subsequent effective p rocessing and presentation of tumor-associated antigens (TAA) peptides to a ctivate TAA-specific helper and cytotoxic T cells. Once the TAA-specific cy totoxic T cells are activated, they can leave the lymph node, circulate in the body, and seek metastatic cells expressing TAA to destroy them. Alterna tively, activated helper T cells may provide the help required for B cells to produce antibodies to TAA on the leukemia or lymphoma cells. Because eve ry patient receives his or her own TAA within the vaccinating cells, such v accines are customized for the patient. These autologous tumor vaccines may be used as an adjuvant treatment that complements currently used treatment regimens by providing the immune system with an additional opportunity to be exposed effectively to autologous TAA.