Oncolytic viruses sensitize human tumor cells for NY-ESO-1 tumor antigen recognition by CD4+ effector T cells.

Abstract

Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1. We show that the co-culture of NY-ESO-1/HLA-DP4 melanoma cells with NY-ESO-1/HLA-DP4 melanoma cells infected and killed by different OV induces an intercellular transfer of NY-ESO-1 that allows the recognition of NY-ESO-1/HLA-DP4 tumor cells by an HLA-DP4/NY-ESO-1-specific CD4+ cytotoxic T cell clone, NY67. We then confirmed this result in a second model with an HLA-DP4+ melanoma cell line that expresses a low amount of NY-ESO-1. Recognition of this cell line by the NY67 clone is largely increased in the presence of OV productive infection. Altogether, our results show for the first time another mechanism of stimulation of the anti-tumor immune response by OV, via the loading of tumor cells with TAA that sensitizes them for direct recognition by specific effector CD4+ T cells, supporting the use of OV for cancer immunotherapy.

Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma

“…An alternative approach to boost the immune response is through antigen agnostic oncolytic virotherapy. Oncolytic viruses represent a new class of therapeutic agents that promote antitumor responses through selective tumor cell killing and the induction of systemic antitumor immunity [10,[32][33][34]. Various genetically modified viruses have been developed as oncolytic agents, and in the present study we used a recombinant MV (Edmonston strain) encoding NIS to treat patients with MM.…”

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

“…234 Moreover, ICD driven by other cellular stressors including RT, photodynamic therapy, extracorporeal photochemotherapy and oncolytic virotherapy is not necessarily associated with the emission of the same DAMPs, cytokines and chemokines. 12,[235][236][237][238] Altogether and in combination with an increased microenvironmental availability of TAAs or TSAs, ICDassociated DAMPs pave the way to: (1) abundant recruitment of antigen-presenting cells (APCs) or their precursors (as in the case of ATP, CCL2, CXCL1, ANXA1) and/or T cells (as in the case of CXCL10) to the tumor microenvironment; (2) efficient phagocytic uptake of dead/dying cancer cells and fragment thereof in the context of immunostimulatory signaling (as in the case of CALR); and, (3) potent functional activation of APCs (as in the case of ATP, HMGB1 and nucleic acids). 12,24,57,113,119,224,237 Ultimately, APCs engulfing TAAs or TSAs and receiving these immunostimulatory cues acquire an extraordinary ability to crosspresent TAA-or TSA-derived epitopes to CD4 + and/or CD8 + T cells in the context of co-stimulation, which enables TAA/TSAtargeting immunity.…”

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

“…6 Tumor cell lysis results in the release of tumor-associated antigens (TAAs) and simultaneous expression of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), which stimulate innate immune receptors on professional antigen-presenting cells (APCs). 7,8 OVs can promote the antitumor T cell response through various mechanisms. For example, they trigger immunogenic cell death in tumor beds, which can promote the maturation and function of dendritic cells (DCs).…”