Oncolytic HSV Vectors and Anti-Tumor Immunity

Abstract

The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune caister.com/cimb 381 Curr. Issues Mol. Biol. Vol. 41 Oncolytic HSV Vectors Glorioso response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment. A. IntroductionRecent advances in cancer therapeutics include the use of tumor-specific lytic (oncolytic) viruses that both debulk tumors -reduce their size by eliminating cancer cells -and break down barriers to the induction of anti-tumor immunity.Oncolytic viruses have been derived from a wide variety of both DNA and RNA virus families, each having unique host ranges and replication mechanisms that make them attractive for attacking different tumor types. Oncolytic virusmediated destruction of tumor cells leads to the production of danger signals by infected cells, a process referred to as immunogenic cell death, and to the release and presentation by antigen presenting cells (APCs) of virus and tumor-derived antigens. Tumor antigenic peptides are created by either an accumulation of mutations in cellular proteins, re-emergence of fetal/testis proteins without complete host tolerance, or by misfolded proteins to create novel processed peptides (

Imunoviroterapia oncolítica com Herpesvírus Simplex tipo I em tumores cerebrais malignos

“…imunidade inata e à apresentação de antigénio favorecida pelas moléculas MHC classe I (Glorioso et al, 2021). As células CD8 T produzem a sua expansão clonal em gânglios linfáticos e baço, migrando subsequentemente para locais de inflamação guiados por quimiocinas (Aldrak et al, 2021).…”

Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms

“…Chemokines and cytokines regulate the trafficking and infiltration of immune cells into the TME. Studies have shown that the infection of OVs elicits potent type I interferon responses (115,116), which can stimulate the production of T cell recruiting chemokines. Inflammatory factors such as tumor necrosis factor (TNF) and interleukin-1b (IL-1b) can also be induced by OVs, which in turn upregulate the expression of selectin on endothelial cells and provide an important signal for T cell infiltration (117)(118)(119).…”

Oncolytic herpes simplex viruses designed for targeted treatment of EGFR-bearing tumors

“…Considerable effort has gone into creating safe and effective herpes simplex virus (HSV) vectors that demonstrate tumor cell–specific oncolysis (oHSV). 1 The oHSV vector talimogene laherparepvec (T-VEC) showed durable responses in 16.3% of melanoma patients following direct intratumoral delivery, 2 and was approved by the US Food and Drug Administration in 2015 for the treatment of solid tumors. 3 T-VEC is attenuated by the deletion of the genes encoding γ34.5 and ICP47, and expresses the human granulocyte-macrophage colony-stimulating factor gene to stimulate an immune response.…”