Galectin-3 defective vaccine for an effective immunotherapy against prostate cancer development

CAROLINA TIRABOSCHI, LUCAS GENTILINI, FELIPE MARTÍN JAWORSKI, ENRIQUE CORAPI, GUSTAVO CARIZO, ANNE CHAUCHEREAU, DIEGO JOSÉ LADERACH AND DANIEL COMPAGNO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Prostate cancer (PCa) is a major problem of health in Argentinaand worldwide. Patients are likely to be cured with early diagnosis,while there is little hope when the cancer is metastatic and resistantto anti-hormonal treatments. Therefore, two alternatives areproposed for castration resistant patients. Depending of the symptomaticor asymptomatic status, chemotherapy based on the use ofTaxol derivatives or, more recently, immunotherapy are proposedrespectively. The latter has generated encouraging results in clinicaltrials, but requires a deeper understanding in order to increase itsefficiency. The main reason for this low efficiency is that tumors developa robust immune response control system.Recent results from our group demonstrate that galectin-3 (Gal-3) is one of the key factors of the immune tolerance in PCa. Usinglentiviral transduced murine TC1 cells expressing stable anti-gal-3shRNA, we demonstrated that tumor cell-expressed Gal-3 wouldact on CD8 + T lymphocytes selectively, without affecting CD4 +T cells, and that inhibiting activation and proliferation of CD8 + Tlymphocytes without inducing their apoptosis. This selective effect isoriginal as compared to the known action of other galectins, such asGal-1. We also observed that low doses of docetaxel (DTX), used inchemotherapeutic treatments of such cancer, leads to the inhibitionof Gal-3 expression in human and murine PCa cells in vitro, but alsoin vivo without distinction of the degree of resistance of the prostatetumors to such chemotherapy. We finally observed that a vaccinecomposed of Gal3-deficient allogeneic PCa cell lysates allows thecontrol of the development of the Gal-3-defective PCa cancer in ananimal model. Thus, in vivo negative regulation of the expressionof Gal-3 in tumors allows us to propose therapeutic alternatives ofimmunotherapy for all PCa patients, including metastatic and castrationand DTX resistant one.