Immunotherapy of Breast Cancer by Antisense Strategy to Type I Insulin-like Growth Factor Receptor (IGF-IR)

ROXANA SCHILLACI; MARIANA SALATINO; JULIANA CASSATARO; CECILIA PROIETTI; GUILLERMO GIAMBARTOLOMEI; MARTÍN RIVAS; ROMINA CARNEVALE; EDUARDO CHARREAU; PATRICIA ELIZALDE

Córdoba. Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

Asociación Latinoamericana de Inmunología

In this study we assessed whether in vivo administration to Balb/c mice of C4HD murine breast cancer cells pre-treated with  phosphorothioate antisense oligodeoxynucleotides (AS[S]ODN) to IGF-IR and irradiated, could provide protection against C4HD wild-type tumor challenge. We also elucidated the mechanism mediating this effect. Immunization of mice with AS[S]ODN-treated C4HD cells resulted in growth inhibition of 53.4%,  61.6% and  60.2% compared to  PBS-treated mice, wild-type C4HD cells injected mice or Sense[S]ODN-treated C4HD cells injected mice respectively. The lack of protection against tumor formation in nude mice indicated T cells involvement. Cytotoxicity and splenocyte proliferation assays showed that a cellular CD8+-dependent immune response acting through Fas/FasL death pathway, could be responsible for the antitumor effect. Immunization induced splenocytes to produce Ag-dependent IFN-ã, indicating a type 1 response. Induction of the immunogenic phenotype in C4HD cells after blocking IGF-IR expression, occurred along with induction of Hsp70 and CD86. This is the first demonstration that breast cancer growth can be inhibited in vivo through induction of a specific immune response with tumor immunogens derived from IGF-IR AS[S]ODN-treated breast tumor cells.