Alphaviruses in Cancer Therapy

Abstract

Alphaviruses have been engineered as expression vectors for different strategies of cancer therapy including immunotherapy and cancer vaccine development. Administration of recombinant virus particles, RNA replicons and plasmid DNA-based replicons provide great flexibility for alphavirus applications. Immunization and delivery studies have demonstrated therapeutic efficacy in the form of reduced tumor growth, tumor regression and eradication of established tumors in different animal models for cancers such as brain, breast, colon, cervical, lung, ovarian, pancreas, prostate cancers, and melanoma. Furthermore, vaccinated animals have showed protection against challenges with tumor cells. A limited number of clinical trials in the area of brain, breast, cervical, colon prostate cancers and melanoma vaccines has been conducted. Particularly, immunization of cervical cancer patients elicited immune responses and therapeutic activity in all patients included in a phase I clinical trial. Moreover, stable disease and partial responses were observed in breast cancer patients and prolonged survival was achieved in colon cancer patients.

A novel three‐plasmid packaging system for chimeric SFV/SIN VRPs derived from Semliki Forest virus and Sindbis virus as a candidate gene delivery vector

“…LR is overexpressed in multiple types of human tumors 8 . Furthermore, because SIN is not associated with a serious human disease, SIN‐derived replicon particles are largely not linked to biosafety concerns 8 . Joan Smyth et al efficiently constructed an infectious chimeric virus of SFV/SIN (spike).…”

“…The recombinant virus particles are mostly called virus‐like particles (VRPs). They are also known as virus‐like replicon particles (VLPs) 8–10 . SFV VRPs have been commonly used for cancer therapy and vaccine development in various animal models, and to some extent, in clinical trials 8,11–13 …”

“…8 Furthermore, because SIN is not associated with a serious human disease, SIN-derived replicon particles are largely not linked to biosafety concerns. 8 Joan Smyth et al efficiently constructed an infectious chimeric virus of SFV/SIN (spike). To construct pSFV/SIN, the regions encoding replicase (nSP1-4) and the capsid were derived from SFV, and the spike-encoding regions were derived from SIN.…”

Local Delivery of Immunomodulatory Antibodies for Gastrointestinal Tumors

“…In addition, local vector administration in the tumor mass potentially limits the infection to cancer cells or tumor-associated cells. With this system, a high and transient expression of the therapeutic gene can be achieved thanks to the self-amplifying nature of the RNA, which promotes the death of the infected cell after 24–72 h. In addition, these vectors induce an important mobilization of the immune system, generating strong IFN-I responses due to the amplification of the viral RNA [ 123 , 129 ]. Therefore, these vectors could be useful to overcome the strong immunosuppression in the TME as well as to promote the release of TAAs, synergizing with other immunotherapies ( Figure 2 ).…”

Alphaviruses in Immunotherapy and Anticancer Therapy

“…In this context, viral vectors have also proven useful for immunotherapeutic applications [ 2 ]. Alphaviruses have frequently been engineered for the overexpression of suitable antigens and immunostimulatory genes for vaccine development and cancer therapy [ 3 ]. Additionally, the expression of cytotoxic and antitumor genes has been used for cancer therapy applications.…”