Cytokine-induced killer cell delivery enhances the antitumor activity of oncolytic reovirus

Abstract

Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery. In this study, CIK cells were successfully loaded with reovirus ex vivo, and viral replication was limited in CIK cells. Confocal microscopy and flow cytometry demonstrated that CIK cells retained reovirus on the surface. Moreover, CIK cells could promote reovirus infection of tumor cells in the presence of neutralizing antibodies; meanwhile, cytotoxicity of CIK cells was increased after loading with reovirus. These findings support further investigation of reovirus and CIK combination for antitumor therapy.

Reovirus enhances cytotoxicity of natural killer cells against colorectal cancer via TLR3 pathway

“…Therefore, combination of reovirus with cytotoxic adaptive cell therapy shows considerable promise as an anticancer therapeutic strategy [ 40 , 41 ]. In previous work, we have shown that cytokine-induced killer (CIK) cells or ex vivo-expanded NK cells can be used as a protective delivery vehicle to carry reovirus to the tumor, avoiding antibody neutralization [ 21 , 42 ]. Moreover, cytotoxicity of CIK cells was increased after loading with reovirus [ 43 ].…”

Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors

“…[222][223][224]226,230,231 Finally, combinations of OV therapy with complementary immunotherapeutic approaches (e.g., ICIs or CAR T, DC and natural killer [NK] cell therapies), have demonstrated enhanced efficacy in preclinical models, and more recently into the clinic, and are actively investigated against multiple indications. 112,128,133,147,187,188,191,[197][198][199]201,203,204,206,207,[232][233][234][235][236][237][238][239][240][241][242][243][244] Not surprisingly, combinatorial regimens involving ICIs are predominant and have already confirmed synergistic effect with several strains of OVs. 112,128,147,187,188,191,[197][198][199][239][240][241]…”

Expression of Concern: Cytokine-induced killer cell delivery enhances the antitumor activity of oncolytic reovirus

“…Following the publication of this article [ 1 , 2 ], concerns were raised that the following panels in Figure 1A appear to partially overlap, despite being used to present different experimental conditions:…”