Dataset Information

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.

ABSTRACT: Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.

SUBMITTER: Tian Y

PROVIDER: S-EPMC8987060 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.

Tian Yaomei Y Xie Daoyuan D Yang Li L

Signal transduction and targeted therapy 20220406 1

Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or ...[more]

PMID: 35387984

Similar Datasets

Project description:New immuno-oncology therapies are improving cancer treatments beyond the former standard of care, as evidenced by the recent and continuing clinical approvals for immunotherapies in a broad range of indications. However, a majority of patients (particularly those with immunologically cold tumors) still do not benefit, highlighting the need for rational combination approaches. Oncolytic viruses (OV) both directly kill tumor cells and inflame the tumor microenvironment. While OV spread can be limited by the generation of antiviral immune responses, the initial local tumor cell killing can reverse the immunosuppressive tumor microenvironment, resulting in more effective release of tumor-associated antigens (TAAs), cross-presentation, and antitumoral effector T cell recruitment. Moreover, many OVs can be engineered to express immunomodulatory genes. Rational combination approaches to cancer immunotherapy include the use of OVs in combination with immune checkpoint inhibitors (ICIs) or adoptive T cell therapy (ACT) to promote sustained antitumoral immune responses. OV combinations have additive or synergistic efficacy in preclinical tumor models with ICIs or ACT. Several preclinical studies have confirmed systemic reactivation and proliferation of adoptively transferred antitumoral T cells in conjunction with oncolytic OVs (expressing cytokines or TAAs) resulting from the specific tumor cell killing and immunostimulation of the tumor microenvironment which leads to increased tumor trafficking, activity, and survival. Recent clinical trials combining OVs with ICIs have shown additive effects in melanoma. Additional clinical data in an expanded range of patient indications are eagerly awaited. The relative timings of OV and ICI combination remains under-studied and is an area for continued exploration. Studies systematically exploring the effects of systemic ICIs prior to, concomitantly with, or following OV therapy will aid in the future design of clinical trials to enhance efficacy and increase patient response rates.

Project description:BackgroundWith few exceptions, current chemotherapy and radiotherapy protocols only obtain a slightly prolonged survival with severe adverse effects in patients with advanced solid tumors. In particular, most solid malignancies not amenable to radical surgery still carry a dismal prognosis, which unfortunately is also the case for relapsing disease after surgery. Even though targeted therapies obtained good results, clinical experience showed that tumors eventually develop resistance. On the other hand, earlier attempts of cancer immunotherapy failed to show consistent efficacy. More recently, a deeper knowledge of immunosuppression in the tumor microenvironment (TME) allowed the development of effective drugs: in particular, monoclonal antibodies targeting the so-called immune checkpoint molecules yielded striking and lasting effects in some tumors. Unfortunately, these monoclonal antibodies are not effective in a majority of patients and are ineffective in several solid malignancies. Furthermore, due to their mechanism of action, checkpoint inhibitors often elicit autoimmune-like disease.Main bodyThe use of viruses as oncolytic agents (OVs) was considered in the past, while only recently OVs revealed a connection with immunotherapy. However, their antitumoral potential has remained largely unexplored, due to safety concerns and some limitations in the techniques to manipulate viruses. OV research was recently revived by a better knowledge of viral/cancer biology and advances in the methodologies to delete virulence/immune-escape related genes from even complex viral genomes or "to arm" OVs with appropriate transgenes. Recently, the first oncolytic virus, the HSV-1 based Talimogene Laherparepvec (T-VEC), was approved for the treatment of non-resectable melanoma in USA and Europe.ConclusionOVs have the potential to become powerful agents of cancer immune and gene therapy. Indeed, in addition to their selective killing activity, they can act as versatile gene expression platforms for the delivery of therapeutic genes. This is particularly true for viruses with a large DNA genome, that can be manipulated to address the multiple immunosuppressive features of the TME. This review will focus on the open issues, on the most promising lines of research in the OV field and, more in general, on how OVs could be improved to achieve real clinical breakthroughs in cancers that are usually difficult to treat by immunotherapy.

Dataset Information

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.

Publications

Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets