It has been shown that lymphocytes, when exposed to interferon-gamma, anti-CD3 antibody, interleukin-1 and interleukin 2, are capable of lysing fresh, non-cultured cancer<unk> s, both primary and metastatic.<unk> <unk> s respond to these lymphokines, particularly IL-2, by lysing tumor<unk> s that were already known to be resistant to NK<unk>  or LAK<unk>  activity. Peripheral blood mononuclear<unk> s or cord blood mononuclear<unk> s are extracted from either peripheral blood or cord blood, e.g. by simple blood draw. Extracted<unk> s are ex-vivo exposed to interferon-gamma, anti-CD3 antibody, interleukin-1 and interleukin-2 in a time-sensitive schedule. These<unk> s strongly stimulate the proliferation and maturation into<unk> <unk> s. After completed maturation<unk> <unk> s are transfused to the donor in autologous settings or to different recipients in allogeneic settings. Furthermore, it has been shown that<unk> <unk> s have a relevant expression of FcγRIIIa (CD16a), which can be exploited in combination with clinical-grade mAbs to redirect their activity in an antigen-specific manner. Indeed, the engagement of CD16a on CD3+CD56+<unk> s led to a potent antibody-dependent<unk> –mediated cytotoxicity (ADCC) both in vitro and in vivo against ovarian cancer.,. Recently, it has been demonstrated the efficacy of a combined approach <unk>  + Cetuximab) against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in mice, and the treatment<unk> <unk> s plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231<unk>  line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by<unk> <unk> s, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic<unk>  population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered<unk> s.
Cytokine-induced killer cell
Natural killer T cell
Natural killer cell
T cell
Regulatory T cell
Memory B cell
Regulatory B cell
Dendritic cell