Major histocompatibility complex (MHC) Class II-positive, invariant chain (Ii)-suppressed tumor cells induce both T helper and cytotoxic T lymphocytes' responses. Genetically controlled immunotherapy could be utilized for prophylactic vaccination of tumor-free individuals who are at high risk of developing tumor and can be therapeutic for treating established tumors that are nonresponsive to existing therapies. In this chapter, we provide practical methods to create a potent in vivo tumor cell vaccine by inducing MHC Class II and Ii using MHC Class II transactivator (CIITA) or interferon-gamma (IFN-γ) and subsequently inhibiting Ii by antisense oligonucleotides. We also describe the development of an adenoviral vector.