H2020Индивидуална стипендия2015–2017

NANOTAM · Development and Evaluation of Nanomedicines for Cancer Treatment through Immunomodulation: Targeting Tumor-Associated Macrophages

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-05-20 → 2017-05-19
Финансиране от ЕС: 168 277 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Наноструктури се разработват, за да насочват лекарствата точно към макрофагите, които подпомагат растежа на туморите. Това помага за промяна на средата около рака, така че тя да спре да подкрепя тумора и вместо това да активира имунната система.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Development and Evaluation of Nanomedicines for Cancer Treatment through Immunomodulation: Targeting Tumor-Associated Macrophages

Recent clinical and experimental research establishes chronic inflammation and immune suppression as dominant effects in the tumor microenvironment. The infiltration of Tumor-Associated Macrophages (TAM) in tumor tissues has been shown to support tumor growth, invasion and metastasis. These discoveries have established the therapeutic targeting of TAM, either by depletion, inhibition of their recruitment or by re-stimulating their cytotoxic function, as one of the most promising approaches to combat cancer. However, up-to-now, these ambitious objectives have not been efficiently achieved, due to a deficient “targeting” and/or “perdurable” dose and “long-lasting” effect of the drugs used at the right location (TAM in the tumor). To address this challenge, this NANOTAM project aims to combine the last advances in the fields of Nanotechnology and Cancer Immunotherapy with the ultimate goal of providing new solutions to the patients with cancer. This NANOTAM project was designed to develop novel Therapeutic Nanostructures (TNs) to improve the specificity of the targeting towards TAM and to increase the effectiveness current antitumoral drugs. Considering the specific molecular characteristics of TAM we have designed on a molecular basis a series of original targeting and therapeutic strategies to reach and re-educate or kill TAM in vivo. The use of nanotechnology in NANOTAM has allowed to address the main challenge of combining the selected molecular strategies in an unique TN. The final goal of this TNs is to re-educate or kill TAM, and consequently, induce the effective switching of the tumor-promoting immune suppressive microenvironment, characteristic of tumors rich in macrophages, to one that kills tumor cells, is anti-angiogenic and promotes adaptive immune responses.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

This project is focused on the development of novel nanomedicines effective in targeting the immunosuppressive, pro-tumoural, Tumour-Associated Macrophages (TAM) with the aim to manipulate the host’s immune system and improve anti-tumour responses. In most patients, chronic inflammation and immune suppression are the dominant effects in the tumour microenvironment. The infiltration of TAM in tumour tissues has been shown to support tumour growth, invasion and metastasis. Indeed, high density of TAM in tumours is correlated with resistance to therapies and poor prognosis. These findings establish TAM as promising targets of future anti-tumour therapies.Here, we aim to design a series of Therapeutic Nanostructures (TNs), containing immunomodulatory or chemotherapeutic compounds, and conveniently functionalized, in order to target and re-educate or kill the TAM. These novel TNs will be composed of biodegradable polysaccharides, i.e. chitosan (CS) or hyaluronic acid (HA), and will be functionalized, with the aim to develop a series of “targeting” strategies to optimally reach TAM in vivo. These strategies involve the chemical linking of: (i) mannose residues expected to direct the TNs to the mannose receptors, highly expressed on the surface of TAM or (ii) the tumour lymphatic-specific peptide (LyP-1), known to have affinity towards NRP1 on TAM. The nanomedicines (TNs) will be loaded with pharmacological activators of TLR7 aimed to re-educate TAM into immunostimulatory anti-tumour macrophages. In the event that re-polarization of TAM is not satisfactory, or its effect is not long lasting in vivo, TNs will be loaded with chemotherapeutic drugs able to kill TAM. The TNs will be tested in vitro and in vivo to verify their effectiveness in switching back the pro-tumoural properties of TAM and their effect on tumour growth. We expect that this approach will enable greater progress in the treatment of tumours and ultimately lead to improved outcomes for cancer patients.

Оригинален текст от CORDIS (на английски).

Участници

HUMANITAS MIRASOLE SPA · Rozzano (Mi)КоординаторИталия