NOVEL RADIOINMUNOTHERAPY FOR METASTATIC COLORECTAL CANCER

CERDA M; GALLINO J; NEVARES N; LOPEZ BULARTE C; TROTTA M; IEZZI ME; GIANNONI F; LLOYD R; CONDE A; ZAPATA A; PODHAJCER O; CRUDO JL; L POLICASTRO

Congreso; Reunion conjunta de las sociedades de biociencias; 2017

Radioimmunotherapy (RIT) is a type of cancer cell targeting therapy which uses monoclonal antibodies against tumorassociatedantigens labeled with radionuclide. The ability for the antibody to specifically bind to a tumour-associated antigensincreases the dose delivered to the tumour cells while decreasing the dose to normal tissues.The epidermal growth factor receptor (EGFR) is expressed in 80% of advanced metastatic colorectal cancer (mCCR) patientsfor witch it is a good antigen to be used in RIT. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to theextracellular domain of EGFR, blocks ligand-induced receptor signaling and modulates tumor-cell growth. Cetuximab incombination with FOLFIRI (irinotecan, 5-Fluorouracil and leucovorin) is a first-line treatment of patients with K-ras mutationnegative(wild-type). In addition, Nanobodies are the smallest (12?15 kDa) intact antigen binding fragments derived fromCamelidae heavy-chain?only antibodies. Particular characteristics such as heat resistant, small size, high solubility, lowimmunogenicity in addition to ability of refolding after denaturation with preserving the binding capacity, make these antigenspecificantibody fragments also very favorable candidate in clinical use. In an other hand, Lutetium-177 (177Lu) is aradionucleide with a half-life of 6,7 days and a maximum negative beta emission of 497 KeV, for which also is ideal for thedevelopment of therapeutic radiopharmaceuticals. The aim of this work is to develop novels EGFR-basedradiopharmaceuticals for mCCR, labeling the monoclonal antibody Cetuximab and a nanobody anti- EGFR (Nb-EGFR) with177Lu. In this work, we describe the obtaining of radioactive immunoconjugates (177Lu-DTPA-Cetuximab) and their specificbinding to cells that overexpress EGFR.