Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.

Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

Wang X ，Shen Y ，Wan X ，Hu X ，Cai WQ ，Wu Z ，Xin Q ，Liu X ，Gui J ，Xin HY ，Xin HW ... -  《Journal of Translational Medicine》

Oncolytic virotherapy as promising immunotherapy against cancer: mechanisms of resistance to oncolytic viruses.

Goradel NH ，Alizadeh A ，Hosseinzadeh S ，Taghipour M ，Ghesmati Z ，Arashkia A ，Negahdari B ... -  《-》

Development of oncolytic virotherapy: from genetic modification to combination therapy.

Lan Q ，Xia S ，Wang Q ，Xu W ，Huang H ，Jiang S ，Lu L ... -  《-》

Emerging systemic delivery strategies of oncolytic viruses: A key step toward cancer immunotherapy.

Oncolytic virotherapy (OVT) is a novel type of immunotherapy that induces anti-tumor responses through selective self-replication within cancer cells and oncolytic virus (OV)-mediated immunostimulation. Notably, talimogene laherparepvec (T-Vec) developed by the Amgen company in 2015, is the first FDA-approved OV product to be administered via intratumoral injection and has been the most successful OVT treatment. However, the systemic administration of OVs still faces huge challenges, including in vivo pre-existing neutralizing antibodies and poor targeting delivery efficacy. Recently, state-of-the-art progress has been made in the development of systemic delivery of OVs, which demonstrates a promising step toward broadening the scope of cancer immunotherapy and improving the clinical efficacy of OV delivery. Herein, this review describes the general characteristics of OVs, focusing on the action mechanisms of OVs as well as the advantages and disadvantages of OVT. The emerging multiple systemic administration approaches of OVs are summarized in the past five years. In addition, the combination treatments between OVT and traditional therapies (chemotherapy, thermotherapy, immunotherapy, and radiotherapy, etc.) are highlighted. Last but not least, the future prospects and challenges of OVT are also discussed, with the aim of facilitating medical researchers to extensively apply the OVT in the cancer therapy.

Ban W ，Guan J ，Huang H ，He Z ，Sun M ，Liu F ，Sun J ... -  《-》

The Role of Oncolytic Viruses in the Treatment of Melanoma.

Bayan CY ，Lopez AT ，Gartrell RD ，Komatsubara KM ，Bogardus M ，Rao N ，Chen C ，Hart TD ，Enzler T ，Rizk EM ，Pradhan JS ，Marks DK ，Geskin LJ ，Saenger YM ... -  《-》