Prime and pull of T cell responses against cancer-exogenous antigens is effective against CPI-resistant tumors

Fulvia Troise; Guido Leoni; Emanuele Sasso; Mariarosaria Del Sorbo; Marialuisa Esposito; Giuseppina Romano; Simona Allocca; Guendalina Froechlich; Gabriella Cotugno; Stefania Capone; Antonella Folgori; Elisa Scarselli; Anna Morena D'Alise; Alfredo Nicosia

doi:10.1016/j.omton.2024.200760

Prime and pull of T cell responses against cancer-exogenous antigens is effective against CPI-resistant tumors

Mol Ther Oncol. 2024 Jan 10;32(1):200760. doi: 10.1016/j.omton.2024.200760. eCollection 2024 Mar 21.

Authors

Affiliations

¹ Nouscom S.r.l, Via di Castel Romano 100, 00128 Rome, Italy.
² Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.
³ CEINGE-Advanced Biotechnologies S.c. a.r.l, Via Gaetano Salvatore 486, 80145 Naples, Italy.
⁴ ReiThera S.r.l, Via di Castel Romano 100, 00128 Rome, Italy.

Abstract

Neoantigen (neoAg)-based cancer vaccines expand preexisting antitumor immunity and elicit novel cancer-specific T cells. However, at odds with prophylactic vaccines, therapeutic antitumor immunity must be induced when the tumor is present and has already established an immunosuppressive environment capable of rapidly impairing the function of anticancer neoAg T cells, thereby leading to lack of efficacy. To overcome tumor-induced immunosuppression, we first vaccinated mice bearing immune checkpoint inhibitor (CPI)-resistant tumors with an adenovirus vector encoding a set of potent cancer-exogenous CD8 and CD4 T cell epitopes (Ad-CAP1), and then "taught" cancer cells to express the same epitopes by using a tumor-retargeted herpesvirus vector (THV-CAP1). Potent CD8 effector T lymphocytes were elicited by Ad-CAP1, and subsequent THV-CAP1 delivery led to a significant delay in tumor growth and even cure.

Keywords: MT: Regular Issue; adenovirus vectors; cancer vaccine; herpesvirus vectors; immune checkpoint inhibitors; neoantigens.