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首页> 外文会议>Conference on Laser Tissue Interaction XIII: Photochemical, Photothermal, and Photomechanical, Jan 20-23, 2002, San Jose, California >Scavenger receptor-targeted photodynamic therapy of J774 tumors in mice: tumor response and concomitant immunity
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Scavenger receptor-targeted photodynamic therapy of J774 tumors in mice: tumor response and concomitant immunity

机译：清除剂受体靶向的J774小鼠光动力疗法：肿瘤反应和伴随的免疫力

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J774 is a cell line derived from Balb/c mice that in vitro behaves as macrophages (including scavenger-receptor expression) and has been widely used to study macrophage cell biology. In vivo it produces histiocytic lymphoma tumors that are invasive and metastatic. We report here on the response of subcutaneous J774 tumors to photodynamic therapy with scavenger-receptor targeted chlorin(e6). Bovine serum albumin was covalently conjugated with chlorin(e6), maleylated and purified by acetone precipitation and both this and free chlorin(e6) were injected Ⅳ into mice at 2mg/kg. When tumors were illuminated with 665nm laser-light after 24 hours there was a highly significant response (tumor volume and growth rate) for the conjugate, but this led to a relatively small survival increase due to the highly metastatic nature of the tumor. The free chlorin(e6) gave very little tumor response. When light was delivered 3 hours after injection the response from the conjugate disappeared due to insufficient time for the tumor cells to take up the photosensitizer by receptor-mediated endocytosis. Free chlorin(e6) at 3 hours however produced a total regression of the tumors due to a primarily vascular effect, but the mice died sooner than control animals. When J774 tumors were surgically removed at different times after implantation the mouse survival was proportional to the length of time they had had the tumor. We interpret this data to show that mice with J774 tumors slowly develop concomitant immunity and a PDT regimen that swiftly ablates the tumor will give worse survival results than a regimen with a slower tumor response.
机译：J774是衍生自Balb / c小鼠的细胞系，在体外表现为巨噬细胞（包括清道夫受体表达），已被广泛用于研究巨噬细胞细胞生物学。在体内它产生侵袭性和转移性的组织细胞性淋巴瘤肿瘤。我们在这里报告皮下J774肿瘤对光动力疗法与清除剂受体针对二氢卟酚（e6）的反应。将牛血清白蛋白与二氢卟酚（e6）共价偶联，通过丙酮沉淀进行马来酰化和纯化，然后将其和游离二氢卟酚（e6）以2mg / kg的剂量静脉注射到小鼠体内。当在24小时后用665nm激光照射肿瘤时，结合物具有非常显着的响应（肿瘤体积和生长速率），但是由于肿瘤的高度转移性，导致存活率相对较小。游离二氢卟酚（e6）对肿瘤的反应很小。在注射后3小时递送光时，由于时间不足以使肿瘤细胞通过受体介导的内吞作用吸收光敏剂，因此来自缀合物的反应消失。然而，由于主要的血管作用，在3小时时游离二氢卟酚（e6）导致了肿瘤的完全消退，但是小鼠比对照组动物更早死亡。当在植入后的不同时间通过手术切除J774肿瘤时，小鼠的存活率与其患肿瘤的时间长短成正比。我们解释该数据以表明患有J774肿瘤的小鼠会缓慢发展伴随的免疫力，而迅速消融肿瘤的PDT方案将比肿瘤反应较慢的方案产生更差的生存结果。

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