ANTITUMOR ACTIVE COMPONENTS OF BCG CELL WALLS

由牛分枝杆菌或M. 污垢杆菌在实验和人类癌症中都具有很强的活性。 免疫疗法。我们的长期目标是识别、隔离 在结构上表征，并在适当的情况下，合成 这些细胞壁的成分是免疫治疗所必需的 活动。由于巨噬细胞的激活在这一过程中非常重要 过程中，我们正在化学水平上检查加工(降解) 巨噬细胞对细菌细胞壁的破坏。这样做的理由是 细菌肽多聚糖的一小段，胞壁二肽，具有 以前被证明具有免疫刺激剂的作用，并作用于 巨噬细胞。这些事实向我们暗示了巨噬细胞的一种机制 参与细菌感染的识别和免疫 放大。我们工作背后的假设是巨噬细胞 会吞噬和分解入侵的细菌，释放 细菌特有的糖肽作为免疫信号 放大。 巨噬细胞对细菌细胞壁的处理正在接受 饲喂放射性标记的氨基糖和枯草杆菌细胞壁 肽聚糖对小鼠巨噬细胞株的氨基酸残基作用 (RAW264)在培养中生长。放射性标记的糖肽是 已被分离、鉴定和分析为巨噬细胞 激活剂。 在这项工作的过程中，我们还观察到其中一个 这些由肽聚糖衍生的糖肽被 巨噬细胞并转化为共价脂质衍生物 (“多肽糖脂”)。我们的初步研究强烈地证明了这一点 作为激烈性疾病的致病因素， 与黄精磷脂部分相关的胚泡形成活性 巨噬细胞暴露于细菌细胞壁。提纯和 该组件的结构表征将是本文的重点 工作。我们还建议分析其对免疫功能的影响，以 包括巨噬细胞杀瘤和杀菌活性以及淋巴细胞 原始细胞的发生和抗体的产生。 这项研究的长期目标是确定佐剂活性 可用于增强巨噬细胞和淋巴细胞功能的化合物 为了加强对恶性肿瘤和微生物的免疫控制 感染。

Preparations consisting of the cell walls of Mycobacterium bovis or M. smegmatis possess potent activity in experimental as well as human cancer immunotherapy. Our long-term objective is to identify, isolate, structurally characterize, and, where appropriate, synthesize the components of these cell walls that are requisite for immunotherapeutic activity. Since macrophage activation is known to be important in this process, we are examining at a chemical level the processing (degradation) of bacterial cell walls by macrophages. The rationale for doing this is that a small fragment of bacterial peptidoglycan, muramyl dipeptide, has previously been shown to function as an immunostimulant and to act upon the macrophage. These facts suggested to us a mechanism for macrophage involvement in the recognition of bacterial infection and in immune amplification. The hypothesis underlying our work is that the macrophage would phagocytize and catabolize an invading bacterium, releasing glycopeptides unique to bacteria to serve as signals for immune amplification. The processing of bacterial cell walls by macrophages is being examined by feeding Bacillus subtilis cell walls radiolabeled in the amino sugar and amino acid residues of peptidoglycan to a murine macrophage cell line (RAW264) grown in culture. The radiolabeled glycopeptides that are excreted have been isolated, characterized, and analyzed as macrophage activators. During the course of this work we also made the observation that one of these peptidoglycan-derived glycopeptides was being retained by the macrophage and converted to a covalent lipid derivative ("peptidoglycolipid"). Our initial studies strongly implicate this peptidoglycolipid as being the agent responsible for the intense blastogenic activity associated with the phospholipid fraction derived from macrophages exposed to bacterial cell walls. The purification and structural characterization of this component will be the focus of this work. We also propose to analyze its effects on immune functions to include macrophage tumoricidal and bacteriacidal activities and lymphocyte blastogenesis and antibody production. The long term goal of this research is to identify adjuvant-active compounds that can be used to potentiate macrophage and lymphocyte function in order to enhance immunological control of malignancy and microbial infection.