H2020Индивидуална стипендия2018–2020

CINK · Advancing cancer immunotherapy using natural killer cells for hematological and metastatic cancers

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

Период: 2018-02-15 → 2020-02-14
Финансиране от ЕС: 158 122 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

NK клетките и механизмите за тяхното активиране се изследват чрез комбиниране на стимулиращи сигнали и блокиране на имунната супресия. Това помага за подобряване на ефективността на имунотерапията срещу кръвни и метастатични ракове, като се намали изтощението на тези клетки.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Advancing cancer immunotherapy using natural killer cells for hematological and metastatic cancers

Cancer immunotherapy has become a powerful weapon for the treatment of cancer in the last decades. Yet the design of an effective immunotherapy is complicated by various factors such as tumor-specific scape mechanisms that renders an immunosuppressive environment, immune-modulating effects of conventional treatments and treatment-related toxicities, all of which results in failure of sustained anti-tumor responses. Therefore, new and more effective approaches are still in much need. NK cells have proven to have a critical role in the immunoediting process by which the immune system controls the progression of cancer cells as well direct cytotoxic functions. Indeed, multiple immunotherapeutic efforts that individually targets the anti-tumor potential of these immune cells have been done with a relative success, but progress still needs to be done. Unfortunately, the development of exhaustion during prolong stimulation as well as tumor NK cell-specific scape mechanisms that reduces NK cell survival and/or functionality, have limited the use of NK cell-based immunotherapy in cancer treatment. Here we are exploring the mechanisms by which NK cell activation is regulated in order to develop strategies that result in sustained and stronger anti-tumor responses while the manifestation of exhaustion is minimized. By combining immune stimulation signals, such as IL-2, IL-12 and/or IL-15 co-stimulation, with inhibition of immunosuppression with immune checkpoint blockade therapy (for example PD1/PDL1, CTLA4 or NKG2A) we expect to improve NK cell efficacy and reduce tumor progression. This project, thus, pretends to unveil the mechanisms regulates NK cell activation to better utilized the potential of these immune cells to prevent metastasis and cancer relapse as well as set up the bases required for its clinical translation.

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

Цел на проекта

The development of monoclonal antibodies (mAb) to target tumor cells has tremendously improve cancer immunotherapy and benefit the treatment of aggressive cancer such as some types of lymphomas, leukemias, multiple myeloma and metastatic cancers. One of the mechanisms of action is the induction of antibody-dependent cellular cytotoxicty (ADCC) through the activation of CD16 on NK cells after binding to the Fc portion of Ab-coated tumor cells. Therefore, strategies that combine NK cell activation and mAb therapy has been intensively explored. However, tumor heterogeneity and unstable expression of the targeted molecule in the tumor cells limits ADCC for mAb therapy resulting in cancer relapse. Furthermore, intrinsic NK immunregulatory mechanisms as well as NK-specific tumor evasion mechanisms have also negatively impacted the use of NK cell-based therapies. In this proposal we will explore the mechanisms involved in the reduced NK cell function (NCF) observed after ADCC and/or NK cell activation (NCA) in order to develop novel strategies to achieve a sustained and stronger NCF by combining stimulating signals with suppression of inhibitory signals such as costimulation via CD137 and IL12, or SHP1/2 blockade. We hypothesize that the adoptive transfer (AT) of NK cells expanded by this novel method will result in better anti-tumor responses after mAb therapy even in tumor cells that express limited amount of the target molecule and limiting consequently cancer relapse rates. Furthermore, due to the overall improvement on NCF, we expect that the combination of AT NK cells with hematopoietic stem cell transplantation (HSCT) will also increase anti-tumor responses; which efficacy up to date has shown to be rather limited. Given the versatility of our approach, this therapy can be used for the treatment of many cancers, but particularly hematological and metastatic cancers and potentially can be translated into the clinic in a short time frame.

Оригинален текст от CORDIS (на английски).

Участници

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