The present invention provides antibodies that bind to CD3 with weak or no detectable binding affinity and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with low affinity and induce human T cell proliferation and hence induce T cell-mediated killing of tumor cells with high efficacy. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3 with weak or no detectable binding affinity in an in vitro assay, and a second antigen-binding molecule that specifically binds human tumor-associated antigen. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing target antigen, such as PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers or other diseases where immunotherapy, i.e. effector cell immunomodulation is warranted.本發明係提供以微弱或未檢出的結合親和力與CD3結合之抗體及彼等之使用方法。根據特定的實施例，本發明之抗體係以低親和力與人類CD3結合並引發人類T細胞增生及因而以高效力引發T細胞-媒介的腫瘤細胞毒殺。根據特定的實施例，本發明係提供雙特異性抗原結合分子，其係包括在活體外分析中以微弱或未檢出的結合親和力與人類CD3特異性結合之第一抗原結合區，及與人類腫瘤-相關抗原特異性結合之第二抗原結合分子。在特定的實施例中，本發明之雙特異性抗原結合分子能抑制表現目標抗原，例如PSMA之腫瘤生長。本發明之抗體和雙特異性抗原結合分子可用於治療其中上調或引發靶向免疫反應為所欲的及/或治療上有利之疾病和病症。例如，本發明之抗體可用於治療各種癌症或其他，其中免疫治療，亦即效應細胞免疫調節證明為正當之疾病。
