Background: : Despite improvements in the treatment of metastatic breast cancer (MBC), there are no curative treatment options. Anti-CD3 monoclonal antibody (mAb) activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi) exhibit anti-HER2 cytotoxicity, proliferate, and secrete immunokines upon tumor engagement. Here we report preliminary results of a phase II immunotherapy trial in which 29 HER2 low expressing(0- 2+) patients (pts) with advanced breast cancer who received infusions of HER2Bi armed ATC (aATC) . Pts were evaluated for time to progression (TTP), overall survival (OS), and immune responses as end points. Methods: Peripheral blood mononuclear cells (PBMC) obtained by leukapheresis were activated with anti-CD3 mAb and expanded with IL-2. aATC were harvested, armed with HER2Bi and cryopreserved in aliquots with a target dose of ≥ 48 billion cells. Pts received oncologist’s choice of chemotherapy (4 cycles or 4 months) followed by 3-4 infusions of aATC. A subset of 5 pts received 250 mg/m²cyclophosphamide to create immunologic space prior to aATC infusions. The median age was 53.5 yrs (range 29-75yrs) with 59% of pts over the age of 50yrs. Results: Nineteen pts were ER positive and had received ≥ 2 lines of endocrine therapy and 16 out of 19 ER positive pts had also received at least 2 lines of chemotherapy for MBC . The overall response rate was 31% defined as stable disease . Anti-tumor immune responses were detected in these pts. The K-M curve for all of the pts who received armed ATC reveals a median OS of 16.7 months (from enrollment). In pts who were evaluable (received ≥ 48 billion aATC), 5 of 16 (31%) were stable at 4 months after all aATC infusions. In pts who received < 48 billion aATC, 2 of 8 (25%) pts were stable at 4 months after aATC infusions. Six severe adverse events (grade ≥3), were documented as probably or definitely related to infusions, in 5 different patients. Conclusions: These clinical results suggest that targeting the high risk HER2 low expressing tumors by this approach may provide survival benefit without excessive toxicity. Clinical trial information: NCT01022138.