Role of ADCC, CDC, and CDCC in Vaccine-Mediated Protection against Her2 Mammary Carcinogenesis
Marco Macagno,
Silvio Bandini,
Elisabetta Bolli,
Amanda Bello,
Federica Riccardo,
Giuseppina Barutello,
Irene Fiore Merighi,
Guido Forni,
Alessia Lamolinara,
Francesco Del Pizzo,
Manuela Iezzi,
Federica Cavallo,
Laura Conti,
Elena Quaglino
Affiliations
Marco Macagno
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Silvio Bandini
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Elisabetta Bolli
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Amanda Bello
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Federica Riccardo
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Giuseppina Barutello
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Irene Fiore Merighi
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Guido Forni
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Alessia Lamolinara
CAST-Center for Advanced Studies and Technology, Department of Neurosciences, Imaging and Clinical Sciences, University G. D’Annunzio of Chieti-Pescara, 66100 Chieti, Italy
Francesco Del Pizzo
CAST-Center for Advanced Studies and Technology, Department of Neurosciences, Imaging and Clinical Sciences, University G. D’Annunzio of Chieti-Pescara, 66100 Chieti, Italy
Manuela Iezzi
CAST-Center for Advanced Studies and Technology, Department of Neurosciences, Imaging and Clinical Sciences, University G. D’Annunzio of Chieti-Pescara, 66100 Chieti, Italy
Federica Cavallo
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Laura Conti
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Elena Quaglino
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy
Amplification or mutation of the Her2 oncoantigen in human mammary glands leads to the development of an aggressive breast carcinoma. Several features of this breast carcinoma are reproduced in mammary carcinomas that spontaneously arise in female transgenic mice bearing the activated rat Her2 oncogene under transcriptional control of the mouse mammary tumor virus promoter-BALB-neuT (neuT) mice. We previously demonstrated that carcinoma progression in neuT mice can be prevented by DNA vaccination with RHuT, a plasmid coding for a chimeric rat/human Her2 protein. RHuT vaccination exerts an antitumor effect, mostly mediated by the induction of a strong anti-rat Her2 antibody response. IgG induced by RHuT vaccine mainly acts by blocking Her2 signaling, thus impairing cell cycle progression and inducing apoptosis of cancer cells, but other indirect effector mechanisms could be involved in the antibody-mediated protection. The recruitment of cells with perforin-dependent cytotoxic activity, able to perform antibody-dependent cellular cytotoxicity, has already been investigated. Less is known about the role of the complement system in sustaining antitumor response through complement-dependent cytotoxicity and cellular cytotoxicity in vaccinated mice. This work highlights that the weight of such mechanisms in RHuT-induced cancer protection is different in transplantable versus autochthonous Her2+ tumor models. These results may shed new light on the effector mechanisms involved in antibody-dependent anti-cancer responses, which might be exploited to ameliorate the therapy of Her2+ breast cancer.
