H2020Индивидуална стипендия2021–2024

Tumour T cells · The fate and therapeutic potential of human neoantigen-specific T cells

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

Период: 2021-09-01 → 2024-03-08
Финансиране от ЕС: 174 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Т-клетките, които разпознават специфични протеини (антигени) на туморите, се анализират, за да се разбере защо често спират да атакуват раковите клетки. Това помага за разработването на по-ефективни имунотерапии, които да повишат процента на успешното лечение при пациентите.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

The fate and therapeutic potential of human neoantigen-specific T cells

Cancer is a leading global health challenge and second highest cause of death worldwide. Despite advancements in treatment, many patients still do not respond effectively to cancer immunotherapies, which are designed to harness the body's immune system to fight cancer. Immunotherapy holds great promise, but its limited success rate means there's a pressing need for better strategies to identify effective targets and overcome the mechanisms that make cancer resistant to treatment. This research aimed to investigate cancer-specific T cells, which are immune cells that can recognize and attack cancer cells, exploring their potential in treating cancer. It also focused on understanding why CD8 T cells, which are crucial for killing cancer cells, often fail in cancer patients. The study sought to identify immunogenic targets by examining cancer antigens—substances that provoke an immune response—in different conditions, including those with acute inflammation and without inflammation. Additionally, the research analyzed the variety of T-cell receptors (TCRs) on tumor-specific CD8 T cells to understand their diversity and potential in fighting cancer. By addressing these objectives, the research aimed to develop more effective cancer immunotherapies, ultimately benefiting patients by increasing treatment success rates and providing new hope in the fight against cancer.

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

Цел на проекта

Cancer is a global health burden and the second leading cause of death worldwide. In recent years, the development of immunotherapy has revolutionised the approach to cancer therapy. A significant limitation, however, is that it is only effective in a subset of patients and the biggest challenges remain the identification of immunogenic targets on human cancers and overcoming immunosuppression. Neoantigens, which are newly formed antigens that arise from mutated tumour proteins, are promising targets in immunotherapy. With the proposed project, we aim to investigate the immune response against human neoantigens which will be induced in a novel humanised tumour mouse model. This unique mouse model harbours the entire human CD8 TCR repertoire and expresses human HLA-2. We will test whether human neoantigens can elicit spontaneous anti-tumour T cell responses in acute inflammatory versus resting conditions, ultimately leading to tumour rejection. We hypothesise that T cells are not able to reject tumours in absence of acute inflammation, similar to the development of most human cancers. To investigate why neoantigen-specific T cells become dysfunctional and fail to reject tumours, we will characterise the functional state and metabolic phenotype of neoantigen-specific T cells by flow cytometry, metabolomics and TCR sequencing. In addition, we will characterise the TCR repertoire of T cells that cause tumour rejection under acute inflammatory conditions. Lastly, we will compare the therapeutic efficacy of adoptively transferred T cells transduced with newly identified TCRs with neoantigen-based vaccines against large established tumours. Overall, this project will contribute to the understanding of immunosurveillance and establish novel techniques to test predicted neoantigens. The identification of human immunogenic targets has the potential to make a global impact on cancer intervention.

Оригинален текст от CORDIS (на английски).

Участници

MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) · BerlinКоординаторГермания