Neoadjuvant Intratumoral Injection of Dendritic Cells in Breast Cancer.
Authors: Minton S. , Gabrilovich D. , Lacevic M. , Laronga C. , Lee M. , Kiluk J. , Khakpour N. , Bui M. , Soliman H. , Ismail-khan R. , Han H. , Munster P. , Janssen W. , Cowan K. , Talmadge J. , Reed E. 
Published: December 2010

Abstract
Backround: Autologous intratumoral dendritic cell injections were used to modulate the tumor reduction effects of standard neoadjuvant chemotherapy. Dendritic cells are important in the regulation of T cell immunity and have been shown to have activity in cancer patients. The neoadjuavant combination therapy was designed to expose dendritic cells to tumor cell apoptosis leading to induction of tumor antigen-specific responses.Methods: Seventeen women with stage II or III breast cancer with breast tumors at least 3 cm in size and had a confirmed initial breast biopsy were entered into this trial from August 2007 through 2009. All patients participating in the clinical trial had tumors that expressed either carcinoembryonic antigen (CEA) or survivin and were HER2-neu negative. They received 4 cycles of paclitaxel at 175 mg/m2 followed by 4 cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 (AC) in a bi-weekly dose dense fashion. Pegfilgrastim 6 mg subcutaneous injection was administered 24 hours after each cycle of chemotherapy. Autologous intratumoral dendritic cell injections were administered one week following the first three paclitaxel treatments. All patients consented to a pre-treatment biopsy and a second tumor biopsy after 4 cycles of paclitaxel to evaluate responses to the intratumoral dendritic cell injections. The endpoints of this trial included assessment of clinical and pathologic response in the breast, safety of the intratumoral dendritic cell injection, evaluation of tumor response, and induction of T cell responses to tumor antigens.Results: Fourteen patients are evaluable for response. The median age was 51.5, the median tumor size was 5.6 cm, and 64 % were estrogen receptor positive. A complete clinical response was observed in 57%, a partial response in 36%, and one stable disease response. A pathologic complete response with no evidence of tumor in the breast was confirmed in 2 patients (14 %). Treatment was well tolerated with no incidence of toxicity observed related to the intratumoral dendritic cell injections. Grade 3/4 hematologic toxicity was as expected for the chemotherapy. Other grade 3/4 toxicity related to the chemotherapy included fatigue, hand-foot, infection, mucositis, and hypocalcemia.Discussion: Combination neoadjuvant therapy with dose-dense paclitaxel followed by AC and autologous intratumoral dendritic cell injections administered between the first three cycles of paclitaxel is safe with no toxicity observed related to the intratumoral dendritic cell injections. Immune response to the treatment is being evaluated by proliferation and interferon-gamma production by peripheral blood mononuclear cells in response to tumor cell lysates, survivin, and CEA. Initial evaluation indicates that treatment resulted in generation of tumor specific responses in more than half of all treated patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4128.