| 摘要 |
<p>Composition (A) for treatment and prevention of bone tumors and metastases that preferentially colonize bone tissue comprises as active agent killed or weakly pathogenic microorganisms that contain a gene for bone sialoprotein (BSP) and can express one or more BSP. The expressed BSP differ from endogenous human BSP of normal osteoblasts in at least one structural feature so that an immune reaction against the altered BSP is generated. Cytostatic. No details of tests for cytostatic activity are given. Vaccine; induction of an immune response against abnormal BSP expressed by tumor cells. Immunization against abnormal BSP protects against attachment of metastatic osteotrophic cells from the primary tumor and induces cell-mediated cytotoxicity against cells that produce the abnormal BSP. (A) are used for treating prostatic, breast, lung, kidney or thyroid tumors; tumors of the blood, lymphatic, cardiovascular, nervous, respiratory, digestive and endocrine systems; tumors of the skin and appendages; of the motor apparatus and of urogenital tract (all claimed). Preferred Materials: The expressed BSP has the altered glycosylation pattern of a BSP expressed by osteotrophic cells of a primary tumor. Especially the active agent in (A) is a foreign protein including a hapten present in human BSP from tumor cells in which the post-translational glycosylation in amino acid residues 120-135 (including the amino acid sequence Thr-Gly-Leu-Ala-Ala) is altered or incomplete, compared with that of the normal human BSP. The specification includes sequences for several preferred peptides for induction of specific antibodies against tumor-associated BSP, e.g. Tyr-Thr-Gly-Leu-Ala-Ala-Ile-Gln-Leu-Pro-Lys-Lys-Ala-Gly-Asp corresponding to positions 124-138 of human BSP, where the Thr residue is not, incompletely or differently glycosylated in the tumor-derived protein. Preferred Microorganisms: These are bacteria, viruses or protozoa, preferably Gram-positive bacteria that replicate internally in host cells, especially Bacillus subtilis; lactobacilli, pseudomonads, staphylococci and Yersinia. Optionally bacteria that do not naturally grow intracellularly are genetically modified with factors that enable them to enter cells, and the microorganisms may include exogenous suicide genes and may also cause a site-directed somatic transgenicity in host cells.</p> |
