- New York NY, US Weiyi WANG - New York NY, US Stewart SHUMAN - New York NY, US Taha MERGHOUB - New York NY, US Jedd WOLCHOK - New York NY, US Wei YAN - Bothell WA, US
Assignee:
MEMORIAL SLOAN KETTERING CANCER CENTER - New York NY
International Classification:
A61K 35/76 C07K 16/28 A61K 9/00
Abstract:
Disclosed herein are methods and compositions related to the treatment, prevention, and/or amelioration of cancer in a subject in need thereof. In particular aspects, the present technology relates to the use of poxviruses, including an engineered attenuated vaccinia vims (VACV) strain comprising a disruption of the N-terminal DNA binding domain of the E3L gene (E3LΔA83N) with a deletion of thymidine kinase (E3LΔ83N-TK) engineered to express an antibody specifically targeting cytotoxic T lymphocyte antigen (E3LΔ83N-TK-anti-CTLA-4), alone or in combination with immune checkpoint blocking agents or immune stimulating agents, as an oncolytic and immunotherapeutic composition. In some aspects, the present technology relates to an E3LΔ83N-TK-anti-CTLA-4 virus further engineered to express human Fms-like tyrosine kinase 3 ligand (hFlt3L) (E3LΔ83N-TK-hFlt3L-anti-CTLA-4). In some embodiments, the engineered viruses are administered to a subject alone or in combination with immune checkpoint blocking agents or immune stimulating agents, as an oncolytic and immunotherapeutic composition.