tailieunhanh - Báo cáo hóa học: " Vaccination with a plasmid DNA encoding HER-2/ neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Vaccination with a plasmid DNA encoding HER-2/ neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial | Norell et al. Journal of Translational Medicine 2010 8 53 http content 8 1 53 RESEARCH JOURNAL OF TRANSLATIONAL MEDICINE Open Access Vaccination with a plasmid DNA encoding HER-2 neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma a pilot clinical trial I I 1 2 n Mr tro 111 2t I C2 Kd D IC hlzo1 am3 A oi 7 A oi4 iriTìCix Prclzino5 D Dio b i lzi4 ndkan Norell Isabel Posciike Jehad diaro vvei Z vvei Courtney Erskine Mane P Piecnocki Keith L Knutson5 Jonas Bergh1 Elisabet Lidbrink1t Rolf Kiessling1 t Abstract Background Adjuvant trastuzumab Herceptin treatment of breast cancer patients significantly improves their clinical outcome. Vaccination is an attractive alternative approach to provide HER-2 neu Her2 -specific antibodies and may in addition concomitantly stimulate Her2-reactive T-cells. Here we report the first administration of a Her2-plasmid DNA pDNA vaccine in humans. Patients and Methods The vaccine encoding a full-length signaling-deficient version of the oncogene Her2 was administered together with low doses of GM-CSF and IL-2 to patients with metastatic Her2-expressing breast carcinoma who were also treated with trastuzumab. Six of eight enrolled patients completed all three vaccine cycles. In the remaining two patients treatment was discontinued after one vaccine cycle due to rapid tumor progression or disease-related complications. The primary objective was the evaluation of safety and tolerability of the vaccine regimen. As a secondary objective treatment-induced Her2-specific immunity was monitored by measuring antibody production as well as T-cell proliferation and cytokine production in response to Her2-derived antigens. Results No clinical manifestations of acute toxicity autoimmunity or cardiotoxicity were observed after administration of Her2-pDNA in combination with GM-CSF IL-2 and trastuzumab. No specific T-cell proliferation following in vitro stimulation of freshly .