Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity

Naturally occurring tumour-binding IgG antibodies are shown to initiate the rejection of allogeneic tumours, whereby Fc-receptor-mediated uptake of tumour immune complexes into dendritic cells activates tumour-reactive T cells, and intra-tumoral injection of allogeneic IgG together with dendritic cell adjuvants induces systemic T-cell-mediated antitumour responses. Tumour rejection by IgG antibodies Cancers generally evade host immune responses yet tumours are not transmissible between individuals, suggesting that the immune system does have the ability to recognize and kill tumour cells. This study of the fate of transplanted allogeneic tumours in mice shows that their rejection is initiated by naturally occurring tumour-binding IgG antibodies. Fcγ-receptor-mediated uptake of tumour immune complexes into dendritic cells activates tumour-reactive T cells, and intra-tumoral injection of allogeneic IgG together with dendritic cell adjuvants induces systemic T-cell-mediated antitumour responses. This work reveals a novel mechanism of tumour rejection that might be exploited clinically. Whereas cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression 1 , 2 , 3 , 4 , 5 , tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection 6 , 7 , 8 , 9 , 10 . How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To a