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Potentiating cancer vaccine efficacy in liver cancer.

ABSTRACT: Hepatocellular carcinoma (HCC) is the most common liver malignancy with a poor prognosis and an overall 5-year survival rate of approximately 5-6%. This is due because standard of care treatment options are limited and none of them shows a sufficient efficacy. HCC is an "inflammation-induced cancer" and preliminary preclinical and clinical data suggest that immunotherapeutic approaches may be a good alternative candidate for the treatment of HCC patients improving the dismal prognosis associated with this cancer. However, recent findings strongly suggest that an optimal immunotherapy in HCC requires the combination of an immune activator with immune modulators, aiming at compensating the strong liver immune suppressive microenvironment. One of the most promising strategy could be represented by the combination of a cancer vaccine with immunomodulatory drugs, such as chemotherapy and checkpoint inhibitors. Very limited examples of such combinatorial strategies have been evaluated in HCC to date, because HCC easily develops resistance to standard chemotherapy, which is also poorly tolerated by patients with liver cirrhosis. The present review describes the most update knowledge in this field.

SUBMITTER: Tagliamonte M

PROVIDER: S-EPMC6169594 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Potentiating cancer vaccine efficacy in liver cancer.

Tagliamonte Maria M Petrizzo Annacarmen A Mauriello Angela A Tornesello Maria Lina ML Buonaguro Franco M FM Buonaguro Luigi L

Oncoimmunology 20180723 10

Hepatocellular carcinoma (HCC) is the most common liver malignancy with a poor prognosis and an overall 5-year survival rate of approximately 5-6%. This is due because standard of care treatment options are limited and none of them shows a sufficient efficacy. HCC is an "inflammation-induced cancer" and preliminary preclinical and clinical data suggest that immunotherapeutic approaches may be a good alternative candidate for the treatment of HCC patients improving the dismal prognosis associated ...[more]

PMID: 30288355

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Project description:BackgroundVaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice.Methodology/principal findingsTowards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo.ConclusionOur results define the immunopotentiating effect of MPL-TDM on protein Ag encapsulated in a controlled release system against experimental VL.

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Potentiating cancer vaccine efficacy in liver cancer.

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Potentiating cancer vaccine efficacy in liver cancer.

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