Systemic Delivery of Oncolytic Adenovirus to Tumors Using Tumor-Infiltrating Lymphocytes as Carriers

Immunotherapy with tumor-infiltrating lymphocytes (TIL) or oncolytic adenoviruses, have shown promising results in cancer treatment, when used as separate therapies. When combination, the antitumor effect is synergistically potentiated due adenovirus infection and its immune stimulating effects on T cells. Indeed, studies hamsters a 100% complete response rate animals were treated coding for TNFa IL-2 (Ad5/3-E2F-D24-hTNFa-IRES-hIL2; TILT-123) TIL therapy. In humans, one caveat virus therapy that intratumoral injection has been traditionally preferred over systemic administration, achieving sufficient concentrations tumors, especially neutralizing antibodies emerge. We previously 5/3 chimeric can bind to human avoidance of neutralization. this study, we hypothesized incubation (TILT-123) TILs prior would allow delivery tumors. This approach deliver both components self-amplifying product. help TILT-123, whose replication will recruit more increase their cytotoxicity. vitro, TILT-123 was seen binding efficiently lymphocytes, supporting idea dual administration. show vivo different models could be delivered tumors carriers.