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DISPARATE SUICIDE CARRIER CELLS FOR TUMOR TARGETING OF PROMISCUOUS ONCOLYTIC VIRUSES

机译:散布的自杀性细胞用于肿瘤性近黏液性病毒的靶向治疗

摘要

The invention provides compositions and methods for treating neoplastic disease, such as cancer, with an oncolytic virus, such as VSV. A carrier cell is used to target a diseased tissue, and to cloak the oncolytic virus from surveillance by the subject's immune system during a targeting interval. Following delivery of the virus to the target tissue, the lysis of the carrier cell, and of the target cell, by the oncolytic virus, promotes an adaptive tumouricidal immune response. A wide variety of disparate carrier cells may be used, in conjunction with a promiscuous oncolytic virus having broad tropism, in an approach which facilitates successive treatments in which a new carrier will not be susceptible to an adaptive immune response mounted against previously used carriers. The promiscuity of the virus also facilitates lysis of carrier cells and target cells that are allogenic or xenogenic. The lytic phase of the carrier cell infection is staged so that the carrier is administered in an eclipse phase, and lysis follows the conclusion of the therapeutic targeting interval.
机译:本发明提供了用溶瘤病毒如VSV治疗肿瘤性疾病如癌症的组合物和方法。载体细胞用于靶向病变组织,并在靶向间隔期间掩盖溶瘤病毒,使其不受受试者免疫系统的监视。在病毒递送至靶组织之后,溶瘤病毒对载体细胞和靶细胞的裂解促进了适应性杀肿瘤免疫应答。可以将多种不同的载体细胞与具有广泛嗜性的混杂溶瘤病毒一起使用,该方法促进了后续的治疗,其中新的载体将不会对针对先前使用的载体的适应性免疫应答敏感。病毒的滥交也促进了异源或异源的载体细胞和靶细胞的裂解。分阶段进行载体细胞感染的溶解阶段,以使载体以蚀相给药,并且裂解遵循治疗靶向间隔的结论。

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