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Cancer treatment: the combination of vaccination with other therapies.

ABSTRACT: Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending on the specific chemotherapeutics. Also, chemotherapy represents one of several options available for clearance of CD4+ Foxp3+ regulatory T cells. Moreover, therapies based on monoclonal antibodies may have synergistic potential in combination with vaccination, both when used for targeting of tumor cells and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system.

SUBMITTER: Andersen MH

PROVIDER: S-EPMC2522294 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

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Project description:OBJECTIVES:To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda. DESIGN:Randomized single-blind controlled trial. SETTING:Tororo, Uganda, an area of high-level malaria transmission. PARTICIPANTS:Children aged one to ten years with confirmed uncomplicated P. falciparum malaria. INTERVENTIONS:Amodiaquine + artesunate or artemether-lumefantrine. OUTCOME MEASURES:Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS:Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether-lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether-lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%-24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether-lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%-25.2%). Amodiaquine + artesunate and artemether-lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens. CONCLUSIONS:Amodiaquine + artesunate and artemether-lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether-lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.

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Cancer treatment: the combination of vaccination with other therapies.

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