The present invention concerns methods and compositions for immunotherapy employing a modified T cell comprising disrupted T cell receptor and/or HLA and comprising a chimeric antigen receptor. In certain embodiments, the compositions are employed allogeneically as universal reagents for “off-the-shelf” treatment of medical conditions such as cancer, autoimmunity, and infection. In particular embodiments, the T cell receptor-negative and/or HLA-negative T cells are generated using zinc finger nucleases, for example.