【摘 要】
：
We have completed four small Phase Ⅰ and Ⅱ clinical trials (a total of 64 patients; 126 doses) using Cytotoxic T Lymphocytes (CTLs) generated against malignant melanoma-specific peptides.We achieved a
【机 构】
：
Drug Discovery Cell Therapy Johnson & Johnson Pharmaceutical R & D, Cell Therapy Team, La Jolla CA
【出 处】
：
BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
We have completed four small Phase Ⅰ and Ⅱ clinical trials (a total of 64 patients; 126 doses) using Cytotoxic T Lymphocytes (CTLs) generated against malignant melanoma-specific peptides.We achieved an overall objective response rate of 18.5%, and 2-year survival rate of 22%.The initial manufacturing protocol used in all four studies had several disadvantages; a manufacturing time of 5 weeks, an extremely labor intensive procedure, an open system of manufacturing, and a product expressing a phenotype which may have been sub-optimal.In an effort to prepare for large-scale Phase Ⅱ/Ⅲ clinical trials, we have incorporated several improvements to the overall manufacturing process.These include: 1) modifying the method of CD8+ T cell isolation, 2) enhancing the primary stimulation with peptide-loaded psoralen/UV treated Drosophila cells expressing human molecules, 3) restimulating effector cells with peptide-loaded antigen presenting cells and autologous feeder cells, 4) including an additional cytokine during ex vivo manufacturing, and 5) enclosing and automating the manufacturing process.These improvements shorten the manufacturing time from 5 weeks to 3 weeks, time critical to these Stage Ⅳ Melanoma patients with a predicted life expectancy of 6-9 months.The availability of this streamlined ex vivo process should allow for commercialization, thereby realizing the promise of cell-based immunotherapy as a treatment for cancer.
其他文献
In the past decades, the incidence of melanoma has risen steadily.Due to prevention efforts, the numbers seem to stabilize in younger age groups.Early diagnosis has increased the proportion of thin me
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lyrnphoma in North America.Response rate of DLBCL to the current empirically developed chemotherapy is only 50-60%.The need for dev
Uveal melanoma is the most common primary intraocular tumor in adults.Despite the advances in diagnosis and treatment of this tumor through the last decades, the mortality rates did not improved consi
Pancreatic cancer, called the silent killer, is the fourth leading cause of cancer-related death in both men and women in US.Due to difficulties in diagnosis and resistance to chemotherapy as well as
Pancreatic adenocarcinoma is among the most aggressive solid malignancies, being the 4th and 6th leading cause of cancer death in the United States and China respectively.Despite its rising incidence,
Accumulating evidences suggest that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth.Recently, there have
Background: Almost 60% of the patients with Acute Myeloid Leukemia (AML) are over the age of 60 years.Age is one of the strongest adverse prognostic factors for AML, both for induction remission and f
The use of goserelin in premenopausal patients is to produce castrated level of estradiol (E2), and the remaining peripheral E2 production is inhibited by letrozole, which would accomplish comparable
Background: Dietary phytochemicals have received considerable attention for their potential in cancer prevention.These phytochemicals must be adequately evaluated in vivo prior to clinical use.Here we
Objectives: Radiographic evaluation may assist in diagnosis and surveillance in women with uterine leiomyosarcoma (LMS).Recent studies have shown that the addition of adjuvant therapy after surgical m