title: Tumor antigen-dependent and tumor antigen-independent activation of antitumor activity in T cells by a bispecific antibody-modified tumor vaccine.
abstract: New approaches of therapeutic cancer vaccination are needed to improve the antitumor activity of T cells from cancer patients. We studied over the last years the activation of human T cells for tumor attack. To this end, we combined the personalized therapeutic tumor vaccine ATV-NDV--which is obtained by isolation, short in vitro culture, irradiation, and infection of patient's tumor cells by Newcastle Disease Virus (NDV)--with bispecific antibodies (bsAbs) binding to this vaccine and introducing anti-CD3 (signal 1) and anti-CD28 (signal 2) antibody activities. This vaccine called ATV-NDV/bsAb showed the unique ability to reactivate a preexisting potentially anergized antitumor memory T cell repertoire. But it also activated naive T cells to have antitumor properties in vitro and in vivo. This innovative concept of direct activation of cancer patients' T cells via cognate and noncognate interactions provides potential for inducing strong antitumor activities aiming at overriding T cell anergy and tumor immune escape mechanisms.
authors.affiliation: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Fournier
authors.forename: Volker
authors.initials: V
authors.lastname: Schirrmacher
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D009522:Newcastle disease virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D018106:CD28 Antigens; D017252:CD3 Complex; D019496:Cancer Vaccines