GALILI, Uri,PICKFORD, Christopher,GRIFFITHS, Graham John Charles
申请号：
GBGB2015/051368
公开号：
WO2015/170121A1
申请日:
2015.05.08
申请国别(地区):
WO
年份:
2015
代理人:
摘要：
The invention relates to pharmaceutical compositions comprising α-Gal BOEL for use in treating patients with tumours. The invention also relates to methods of treating tumours using said compositions. The invention discloses that following intratumoural injection of α- Gal BOEL, binding of the natural anti-Gal antibody to de novo expressed tumoural α-Gal epitopes induces inflammation resulting in an anti-Gal antibody mediated opsonization of tumour cells and their uptake by antigen presenting cells. These antigen presenting cells migrate to draining lymph nodes and activate tumour specific T cells thereby converting the treated tumour lesions into in situ autologous tumour vaccines. This therapy can be applied to patients with multiple lesions and in neo-adjuvant therapy to patients before tumour resection. In addition to the regression and/or destruction of the treated tumour, such a vaccine will help in the immune mediated destruction of micrometastases that are not detectable during the removal of the treated tumour. The invention further teaches the enhancement of anti-tumour α-Gal BOEL treatment by the use of antibodies that inhibit the activity of immunological checkpoints molecules.Linvention concerne des compositions pharmaceutiques comprenant de lα-Gal BOEL pour son utilisation dans le traitement de patients présentant des tumeurs. Linvention concerne également des procédés de traitement de tumeurs utilisant lesdites compositions. Selon linvention, à la suite dune injection intratumorale dα-Gal BOEL, la liaison de lanticorps anti-Gal naturel à des épitopes dα-Gal tumoraux exprimés de novo provoque une inflammation résultant en une opsonisation médiée par lanticorps anti-Gal de cellules tumorales et leur absorption par des cellules présentatrices dantigènes. Ces cellules présentatrices dantigènes migrent vers les ganglions lymphatiques de drainage et activent les lymphocytes T spécifiques des tumeurs, convertissant ainsi les lésions tumorales traitées en vac
