Combination therapy for cancer
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.
Keywords
Immune, cancer, T cells, natural killer, chemotherapy agents, doxorubicin, b-AP15, pre-treatment, pre-clinical, clinical trials