H2020Индивидуална стипендия2018–2019

THAT IS HUNT · Triggering Haematological Adoptive T-cell Immunotherapy Strategies by HUnting Novel T-cell receptors

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

Период: 2018-01-01 → 2019-12-31
Финансиране от ЕС: 168 277 €
Участници: 1
Схема: MSCA-IF-EF-SE

Линиите свързват координатора с партньорите.

Накратко на български

Нови рецептори на Т-клетките се търсят, за да разпознават и атакуват специфични антигени при острия миелоиден лейкоз. Това помага за създаването на терапии, които унищожават раковите клетки, без да увреждат здравите тъкани на пациента.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Triggering Haematological Adoptive T-cell Immunotherapy Strategies by HUnting Novel T-cellreceptors

Acute myeloid leukemia (AML) is an aggressive malignancy, still largely incurable. AML can be cured by allogeneic hematopoietic stem cell transplantation (HSCT), indicating that the disease is sensitive to immunotherapy. The efficacy of this therapeutic approach is partially related to the Graft versus Leukemia (GvL) effect, the ability of the allogeneic immune system to mount an immune response towards cancer cells. Unfortunately, the GvL effect is often counterbalanced by the onset of an inflammatory reaction against healthy tissues (Graft versus Host Disease, GvHD). Several strategies have been pursued with the aim of decreasing GvHD while benefiting of GvL. With these procedures, GvHD decreased but the immune reconstitution was slower with a consequent increase of the infection rate and of disease relapse. New treatments are needed, and adoptive T cell therapy may represent a promising approach. The infusion of T cells specifically able to recognize tumor antigens can mediate leukemia eradication while avoiding GvHD. Furthermore, it is nowadays possible to completely abrogate the endogenous T cell receptor (TCR) repertoire and to redirect T cell specificity towards tumor cells, further increasing the potential for human therapeutics of TCR-engineered T cells. What is then limiting the wide range exploitation of T cell-based immunotherapeutic approaches? To generate a potent and clinically relevant T cell engineered product, the identification of novel epitopes and the hunting of novel TCRs is fundamental. With the THAT IS HUNT proposal, we are addressing the paucity of tumor-specific TCRs currently available by exploiting a “from bed to benchside and back approach”. The plan was to identify in vitro a collection of novel TCRs and tumor epitopes by taking advantage of a) intrinsic biological features of the leukemic blasts, b) omics technologies and c) high dimensional flow cytometry.

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

Цел на проекта

Recent encouraging clinical results obtained with engineered T lymphocytes and increasing advances in the genome editingfield, have opened new opportunities for T-cell receptor (TCR) gene therapy as an immunotherapeutic approach for cancer.Unfortunately, the broad applicability of this treatment is still hampered by the possible mispairing of exogenous/endogenousTCR chains and by the limited number of high avidity tumor-specific TCRs. While the first issue has been successfullyaddressed by the hosting lab with the development a TCR gene editing protocol, the identification of novel tumor-specificTCRs is urgently required and this is the aim of my research proposal. We have the unique opportunity to combine the highlycomplementary expertise of the hosting lab in T-cell biology/genetic transfer and of the applicant on immune repertoiresequencing. We will target acute myeloid leukemia (AML) and hypothesize that by exploiting intrinsic features of AML (i.e.ability of AML blasts to differentiate into potent antigen presenting cells expressing tumor antigens), the functional fingerprintinduced by AML on tumor-reactive T-cells, and cutting-edge technologies (i.e. next generation sequencing; ligandomelandscape analysis), we will provide a comprehensive immunoprofiling of tumor-specific T-cells and isolate tumor TCRspecificities. Results obtained in this study will streamline TCR hunting studies in solid tumors, leading to the generation of aTCR library for different antigens and HLA restrictions, thus rendering TCR gene editing an innovative off-the-shelftreatment available for a high number of cancer patients. Awarding this fellowship will greatly enhance researcher’s careernot only by providing the opportunity to widen scientific knowhow and acquire new skills, but also by enabling the researcherto address a major bottleneck currently limiting the full exploitation of the rapidly growing field of cancer immunotherapy.

Оригинален текст от CORDIS (на английски).

Участници

OSPEDALE SAN RAFFAELE SRL · MilanoКоординаторИталия