BraINstorm · Engineered nanocarriers for simultaneous anticancer immune response and “switching” of tumor-associated macrophages for intranasal glioblastoma treatment
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2020-09-01 → 2022-08-31
- Финансиране от ЕС
- 166 320 €
- Участници
- 1
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Наноносители за intranasal доставка на имунотерапия се тестват за лечение на глиобластом, най-агресивния мозъчен тумор. Това е важно, защото кръвно-мозъчната бариера пречи на стандартната химиотерапия да достигне до клетките на рака.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Engineered nanocarriers for simultaneous anticancer immune response and “switching” of tumor-associated macrophages for intranasal glioblastoma treatment
Glioblastoma (GBM) is the most common, aggressive, and neurological destructive primary brain tumour in adults, among the most lethal human malignancies. An estimated 8-10,000 cases of GBM are diagnosed (in both sexes) every year. The current treatment includes safe maximal surgical resection of the accessible tumour followed by radiotherapy and chemotherapy combined with corticosteroids after three to four weeks. However, this approach is highly invasive, and not always applicable (40% of patients have unresectable GBM). Despite the invasive treatment, the prognosis for GBM is very poor and the patient's median survival is 14.6 months. Reasons behind the inefficacy of therapy against GBM reside in its anatomical location (the blood-brain barrier (BBB) precludes the passage of the majority of chemotherapy agents to the brain) and its aggressive tumour immune microenvironment (TIME) that plays a significant role in GBM progression and diffusion by stimulating angiogenesis and cell migration. In this context, immunotherapy has emerged as a potentially efficient means to treat cancers by turning the immune system against tumour cells. Notable progress in the field of immunotherapy has been made, particularly with the use of tumor vaccines; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines and tumor cell vaccines. Despite the impressive progression of immunotherapeutics and vaccination strategies, GBM remains a "cold," resistant, and deadly cancer. One solution is to break with traditional drug development paradigms and engineer the delivery of immunotherapeutics to target tissues (GBM or lymph nodes) or cell types to control the timing/location of immunomodulation. To achieve this goal, nanomedicine-based approaches offer a means to increase immunotherapeutic efficacy. Due to the high incidence of GBM in European citizens and the observation of 70% of cases in patients between 45 and 70 years, the need for new therapeutic approaches will have significant social, clinical, and economic relevance and impact. Furthermore, the socioeconomic burden of GBM will be reduced by diminishing side effects and treatment costs. We also speculate that our strategy can be translated into other cancer types lacking immunotherapy approaches (e.g., brain metastasis and pediatric tumours). We developed the proposed research project with the knowledge that innovation alone is not sufficient for the development of an original scientific project; we must also answer patient needs and impact lifestyles.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Glioblastoma (GBM) remains a non-curable disease due to its high complexity and its position beyond the blood-brain barrier, which precludes access by conventional therapies. The current standard of care includes tumor resection surgery followed by radiotherapy or chemotherapy; an invasive process with a survival rate after five years is less than 5%. Tumor-associated macrophages (TAM) type 2 (M2 macrophages) comprise 30-50% of the infiltrated cells in GBM microenvironment and support tumor expansion. Immunotherapy represents an appealing strategy to treat several cancer types by turning the immune system against tumor cells; tumor antigen peptides (TAAs) recently emerged as an immunotherapeutic approach that can provide for a long-lasting immune response. Immunomodulatory oligonucleotides can “switch” M2 macrophages into M1 macrophages that produce an anti-tumoral effect. The BraINstorm (Brain INtranasal storm) project aims to engineer a hyaluronic acid (HA)-based combination conjugates that tackle GBM by the stimulation of the immune system via the delivery of TAAs and an immunomodulatory oligonucleotide (CpG) that promotes M2 macrophage “re-education” generating an “anticancer storm”. In parallel, taking advantage of the intrinsic muco-adhesivity of HA, BraINstorm will explore the nose-to-brain drug delivery, a more patient-friendly route that reduces the invasiveness. Novel combination immunoconjugates will be fully chemical-physical characterized and preliminary in vitro studies will be performed assessing the biocompatibility, drug release, and nasal mucosa barrier crossing in an ex-vivo model. Finally, the prophylactic and therapeutic activity of the HA-based conjugates will be in vivo explored in a clinically relevant GBM in vivo model through intranasal (IN) and local treatment administration with regards to effects on tumor size, immune memory, and survival.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITE CATHOLIQUE DE LOUVAIN · LOUVAIN LA NEUVEКоординаторБелгия
Връзки
Данни: CORDIS, © Европейски съюз
