Immunotherapeutic methods and compositions are contemplated in which neoepitopes and/or tumor associated antigens are delivered to dendritic cells via an adenoviral expression system that targets MHC-I and/or MHC-II presentation systems and that further provides one or more recombinant peptides to stimulate T cell activation and interfere with checkpoint inhibition. Treatment is further supported by transfusion of NK cells, which may be modified to have a high affinity CD 16 receptor and/or a chimeric antigen receptor that binds to one or more neoepitopes and/or tumor associated antigens.