Heterologous polyclonal antibodies (pAb) were shown to possess oncolytic properties a century ago with reported clinical responses. More recent pre-clinical models confirm pAb efficacy though their ability to tackle complex target antigens, which reduces susceptibility to tumor escape. Owing to the recent availability of glyco-humanized pAbs with acceptable clinical safety profile, we revisited use of pAbs in oncology and highlighted their therapeutic potential against multiple cancer types.Murine anti-tumor pAbs were generated after repeated immunization of rabbits with murine tumor cell lines from hepatocarcinoma, melanoma, and colorectal cancers. Anti-tumor pAbs recognized and showed cytotoxicity against their targets without cross-reactivity with healthy tissues. In vivo, pAbs are effective alone, moreover, these pAbs synergize with, immune checkpoints inhibitors like anti-PDL-1 in several cancer models. They elicited an anti-tumor host immune response and prevented metastases.The anticancer activity of pAbs was also confirmed in xenografted NMRI nude mice using glyco-humanized pAbs (GH-pAbs) produced by repeated immunization of pigs with human tumor cell lines.In conclusion, the availability of bioengineered GH-pAb allows to revisit passive immunotherapy with oncolytic pAb to fight against solid tumor and cancer metastasis.