CHEMO-IMMUNE THERAPY

A translational approach evaluating novel strategies using chemotherapy to enhance immune-mediated anti-tumor activity

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 Obiettivo del progetto (Objective)

'A wealth of successful pre-clinical immunotherapy-based treatment protocols against cancer have been documented, yet only a limited number of clinical trials have proven to be successful. A common consensus among clinical and bench-side researchers is that a combination of several treatment modalities should be used to achieve complete tumor regression. In recent years, evidence that chemotherapy agents can be used to enhance immune-based therapies has emerged. The specific aims described below are designed to evaluate novel treatment modalities against cancer using chemotherapy agents that have the ability to sensitize tumors to both innate and adaptive anti-tumor immune responses. 1. Examine the effect of different chemotherapy agents in their ability to modify tumor susceptibility to autologous and allogeneic natural killer (NK) and T cell -mediated apoptosis in vitro. 2. In vivo confirmation and evaluation of selected agents in murine syngeneic and allogeneic hematopoietic stem cell transplantation (HCT) tumor models. The results of these studies will lay a foundation for NK cell-based and T cell-based therapies which could lead to more effective treatments for cancer patients. In addition to defining mechanisms how the various chemotherapy agents may influence NK or T cell anti-tumor responses, several subsidiary projects derived from this research will most likely develop.'

Introduzione (Teaser)

The immune system plays a key role when it comes to fighting infections or preventing diseases. This is particularly important in the fight against cancer.

Descrizione progetto (Article)

Presence of immune cells such as T cells and natural killer (NK) cells in tumour sites has been linked to favourable outcomes in cancer patients. Research has also shown that chemotherapy agents increase the sensitivity of cancerous cells to immune cells to facilitate death of cancer cells.

The EU-funded CHEMO-IMMUNE THERAPY project evaluated the ability of different chemotherapy agents to sensitise tumour cells to combined therapy with T and NK cells.

To begin with, scientists isolated NK and T cells from melanoma patients and tested for anti-cancer activity on different cancer cell lines in vitro. Over a dozen chemotherapy agents were screened to assess their tumour-sensitising ability to immune cells. Out of these, anthracyclin, doxorubicin and the proteasome inhibitor b-AP15 proved to be consistently effective.

Besides in vitro tests, in vivo tests on mice with cancer were also performed to assess the effect of pre-treatment with doxorubicin or b-AP15. Both agents successfully increased sensitivity of cancer cells to immune cells without affecting normal cells. Combined infusion of NK and T cells in cancerous mice that were pre-treated with chemotherapy showed a significant increase in survival and reduced tumour progression.

Successful clinical trial outcomes may improve the prognosis of most cancer patients through such combination therapies.