H2020Индивидуална стипендия2017–2019

GLIOMA · Targeting Glioblastoma using Combinatorial Therapeutic Nanovaccine

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

Период: 2017-10-02 → 2019-10-01
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

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Накратко на български

Глиобластомата е агресивен мозъчен тумор, при който се тества нановакцина от златни нанокаже, комбинираща химио- и имунотерапия. Това е важно, защото някои ракови клетки са устойчиви на стандартното лечение, което често води до повторно развитие на болестта.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Targeting Glioblastoma using Combinatorial Therapeutic Nanovaccine

Glioblastoma (GBM) is one of the major malignant brain tumors seen. Patients with GBM and brain metastasis currently have less treatment options available. Existing therapies have many difficulties in the complete killing of GBM cells as they possess a mixed grade of cells. Certain cells within these highly malignant tumors may respond to primary therapies while others do not. GBMs are aggressive in nature with a near sure recurrence despite aggressive surgical resection and combinatorial chemoradiation. Increasing evidence suggests that these tumours harbour a brain tumour-initiating cell population that is resistant to radiation and current standard chemotherapy. Interestingly, this highly malignant population can be identified by specific cell markers. In this project a combinatorial strategy that represses tumour immune-evasion, and specifically targets the cancer cells which potentially could hinder recurrence and provide clinical benefit to glioma treatment was studied. The combination of immunotherapy with chemotherapy could enhance the antitumor efficacy by activating multilevel cancer killing mechanisms. The main objectives of the project objectives were: i) development of a multipotent theragnostic nanovaccine (TNVax) for targeting GBM using hollow gold nanocages; ii) assessment of the anticancer potential of TNVax nanoparticles, and iii) assessment of the drug delivery and therapeutic efficiency of TNVax. Combinatorial nanotherapeutics, implemented in project, is a novel idea for introducing targeted therapies to cancer killing. The project Glioma has foreseen the future of therapeutics and has conceptualized and executed a novel strategy in the field of nanodrug delivery. By combining chemo and immuno parameters in the same system, TNVax has shown the future of combination therapeutics. The TNVax prototype based on the gold nanocages has shown an ideal prototype feature for the formation of multi-functionalised nanoformulation possible for the targeted cancer therapy. The results have suggested the successful killing of glioma cells under invitro conditions with enormous characterisation techniques performed. The future prospects will be to enhance the release mechanism of drug from the complex followed by studying its efficacy and immunomodulation studies in real systems.

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

Цел на проекта

The proposal aims at the synthesis, characterisation and application of a novel therapeutic nanovaccine (TNVax) that holds multiple modules for targeting glioblastoma multiforme (GBM). The proposed TNVax formulation includes a gold nanocage core encapsulating Temozolamide (TMZ), coated with an extremophilic bacterial polysaccharide, mauran functionalised with anti-PD-L1 antibody and anti-CD133 antibody. The us of NVax nanoparticles (NPs) offers a combinatorial approach in killing GBM cells both by immuno- and chemo- therapeutically. Site-specific delivery of the payload will stimulate the host immune system and channel the immune cells to the target site. Functionalisation of the anti-PD-L1 antibody on drug-encapsulatedNPs would significantly alter the immune suppression caused by GBM cells on TNVax delivery. In addition to anti-PD-L1 antibody, the TNVax particles contain tumour specific monoclonal antibody that specifically recognizes CD133 antigen and facilitates strong binding. This approach would enhance the amount of antitumour activity offered by multiple means and thereby leaving a strong immune response against GBM based on antigen-antibody interactions. TNVax NPs will be synthesised and characterised using microscopic and spectroscopic techniques and then subjected to in vitro and in vivo evaluations. In vitro studies will be performed for drug release kinetics and cytotoxicity using immunofluorescence and FACS analysis. Induction of immune response by TNVax NPs will be evaluated using macrophage activation, induction of T-cell activity and cytokine production under in vitro conditions. The pharmacokinetic and pharmacodynamic studieswill be carried out and histopathological examinations performed using appropriate murine models induced with GBM cell lines. The potential outcomes of the proposed studies will help patients who suffer from early and advanced GBM by eradicating the disease permanently and leaving good immunological memory.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITY OF BRIGHTON · BrightonКоординаторОбединеното кралство