Sconocchia AIRC2021 Targeting Head and Neck cancer by anti-B7-H3 mAb and CD64-T cells: implication in prognosis and therapy (DSB.AD007.233)

Area tematica

Scienze biomediche

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Farmacologia Traslazionale (IFT)

Responsabile di progetto

GIUSEPPE SCONOCCHIA
Telefono: 0649934220
E-mail: GIUSEPPE.SCONOCCHIA@IFT.CNR.IT

Abstract

The goal is to demonstrate that CD64-CR T cells armed with the mAb 376.96 plus an anti-PD-L1 and sonidegib represent effective cell-based immunotherapy of SCCHN. Aims We will test the following hypothesis: B7-H3 expression is a prognostic marker of the disease;CD64-CR T cells armed with the mAb 376.96 and an anti-PD-L1, and sonidegib can eliminate SCCHN HPV+ and HPV-cells under nonhypoxic and hypoxic condition in vitro and in NSG mice grafted with SCCHN cell lines; the results obtained with SCCHN cell lines have clinical relevance, as they are reproduced in NSG mice orthotopically grafted with patient-derived SCCHN xenografts (PDX) mouse-CD64-CR T cells with the mAb 376.96 do not cause detrimental effects when injected to syngeneic immunocompetent mice. .CD64-CR is compared to a classical B7-H3-CAR. CD64-CR is composed of the extracellular portion of CD64.This molecule is Both cloned with the human CD8 transmembrane, the CD28 intracytoplasmic domain, and the TCR/CD3 zeta chain. The transgene cassette is cloned into the SFG retroviral backbone. Following the production of the retroviral supernatant, T cells are transduced. CD64-CR T cells are loaded with the mAb 376.96.

Obiettivi

Hypothesis
The goal of this application is to demonstrate that CD64-CR T cells armed with the mAb 376.96 plus an anti-PD-L1 and
sonidegib will allow the designing of effective cell-based immunotherapy of SCCHN.
Aims
We will test the following hypothesis: 1) B7-H3 expression is a prognostic marker of the disease (12 months); 2) CD64-CR T
cells armed with the mAb 376.96 and an anti-PD-L1, and sonidegib can eliminate SCCHN HPV+ and HPV-cells under
nonhypoxic and hypoxic condition in vitro and 3) in NSG mice grafted with SCCHN cell lines (18 and 14 months); 4) the
results obtained with SCCHN cell lines have clinical relevance, as they are reproduced in NSG mice orthotopically grafted with
patient-derived SCCHN xenografts (PDX) (16 months); 5) mouse-CD64-CR T cells with the mAb 376.96 do not cause
detrimental effects when injected to syngeneic immunocompetent mice (12 months).

Data inizio attività

01/01/2021

Parole chiave

Head and neck ca, Target therapy, Prognosis; Immunotherapy; Cytotoxic T Lymphocytes (CTL

Ultimo aggiornamento: 27/07/2024