Tumor antigen-dependent and tumor antigen-independent activation of antitumor activity in T cells by a bispecific antibody-modified tumor vaccine.

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.