The present application provides oncolytic vaccinia virus encoding an immune checkpoint modulator, such as immune checkpoint inhibitor, wherein the expression of the immune checkpoint modulator is driven by a late promoter. The present application also provides oncolytic virus encoding an immune checkpoint modulator, and a bispecific molecule comprising antigen-binding domains specifically recognizing a tumor antigen and a cell surface molecule on an effector cell, such as CD3 on T lymphocytes. In some embodiments, the oncolytic virus further encodes a cytokine. Methods of treating cancer using one or more of the compositions are encompassed in the disclosure.本申請案提供編碼免疫檢查點調節子(諸如免疫檢查點抑制劑)之溶瘤牛痘病毒,其中該免疫檢查點調節子之表現係由晚期啟動子驅動。本申請案亦提供編碼免疫檢查點調節子及雙特異性分子之溶瘤病毒,該雙特異性分子包含特異性識別腫瘤抗原及效應細胞上之細胞表面分子(諸如T淋巴細胞上之CD3)的抗原結合結構域。在一些實施例中,該溶瘤病毒進一步編碼細胞介素。本發明中涵蓋使用一或多種該等組合物治療癌症的方法。
