Alphavirus-based delivery of chitinase-like-protein gene for anti-tumour programing of macrophages (Alpha-Chit)
Project title: "Alphavirus-based delivery of chitinase-like-protein gene for anti-tumour programing of macrophages (Alpha-Chit)"
Funding: ERA-NET Rus Plus (Further linking Russia to the ERA: Coordination of MS/AC S&T programmes towards and with Russia)
Project No.: BMC nr. PRL/16/9
Period: 36 months (1st January 2016 – 30st June 2018)
Partners: UHEI - Ruprecht-Karls Universität Heidelberg (Germany), TSU - Tomsk State University (Russian)
Principle Investigator: Dr.biol.Anna Zajakina
Development of anti-tumour drugs is a highly relevant and timely aim of biotechnology considering aging of the population and increasing socio-economic significance of cancer. Targeting only cancer cells is insufficient to stop tumour growth and metastatic spread. Recent data indicate that tumour microenvironment is essential regulatory component deciding about tumour progression. Tumour-associate macrophages (TAM) constitute a key regulatory component of tumour microenvironment. Tumour cells program TAM for their needs to support tumour cell proliferation, angiogenesis and metastasis. However, TAM possess all the necessary tools to stop tumour progression. The most advance approach to instruct macrophages to stop supporting tumour progression and to act against tumour is their functional reprogramming. The members of the consortium previously have identified SI-CLP as a novel tumour suppressor that inhibits tumour supporting functions of TAM in pre-clinical animal model. The goal of the current multidisciplinary collaborative project is to design an efficient and safe gene therapy approach to deliver SI-CLP to tumour sites and to increase the SI-CLP anti-tumour properties by introducing additional mutations to enhance TAM reprogramming effect. For the delivery of SI-CLP into tumour we will design advanced alphavirus based vectors and examine them in in vivo and ex vivo preclinical experimental models for the TAM reprogramming and suppression of tumour progression. By analysis of clinical material from patient with breast and colon cancer we will identify the range of tumour stages for the therapeutic interventions. Alpha-Chit will result in an innovative gene therapy approach to activate anti-tumour functions of TAM that can be used alone or in combination with chemotherapy.