DENDRITIC CELLS ACTIVATED BY GMCSF & IL4 AS A TUMOR VACCINE IN ADVANCED CANCER

我们已经描述了树突状细胞（DC）的产生和使用，以刺激特异性T细胞对确定的抗原以及肿瘤裂解物的反应。 在临床前研究中，从人外周血中获得的组织培养的DC的富集群体可以在体外刺激T细胞对破伤风类毒素、白色念珠菌和匙孔血蓝蛋白（KLH）的有效的、特异性的初级和次级增殖反应。 在小鼠模型中，从脾脏分离或从骨髓产生的肿瘤脉冲DC在体外和体内刺激特异性抗肿瘤T细胞对弱免疫原性和低免疫原性肿瘤的反应性方面非常有效。 这些临床前研究为用肿瘤裂解物和KLH脉冲的人DC用于晚期癌症成人患者的临床评价提供了依据。 拟定的临床研究将根据FDA批准的IND（BB-IND# 6958，提交给MulD，P.I.博士）进行。"

We have described the generation and use of dendritic cells (DC) to stimulate specific T cell responses to both defined antigens as well as tumor lysates. In preclinical studies, an enriched population of tissue cultured DC obtained from human peripheral blood could stimulate potent, specific primary and secondary proliferative responses of T cells to tetanus toxoid, candida albicans, and Keyhole limpet hemocyanin (KLH) in vitro. In mouse models, tumor-pulsed DC isolated from spleen or generated from bone marrow were highly effective in stimulating specific antitumor T cell reactivities to weakly- and poorly-immunogenic tumors both in vitro and in vivo. These preclinical studies serve as rationale for a clinical evaluation of human DC pulsed with tumor lysate and KLH for adult patients with advanced cancer. The clinical studies proposed will be conducted under an FDA-approved IND (BB-IND# 6958 to Dr. MulD, P.I.)"