Cytokine gene transfer in cancer therapy

Cao, Lei; Kulmburg, P; Veelken, Hendrik; Mackensen, Andréas; Mézes, Beata; Lindemann, A.; Mertelsmann, Roland; Rosenthal, Felicia M.

doi:10.1002/stem.5530160831

Cited by 14 publications

(7 citation statements)

References 68 publications

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“…However, inflammation is a critical component of tumor progression and tumor microenvironments are controlled by inflammatory cells. Tumor cells activate specific signaling molecules in the innate immune system, including cytokines, chemokines, and their receptors during invasion, migration, and metastasis [7,8,9]. Therefore, recent cancer therapies have targeted immune modulation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

et al. 2013

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Natural killer (NK) cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA) and eicosapentaenoic (EPA) acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA) on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day) or DHA (240 mg/kg BW/day) were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG) E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.

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Section: Introductionmentioning

confidence: 99%

Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

et al. 2013

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“…HCC is believed to be a potentially ideal tumor for targeting by immune-based therapies; 15 the immunotherapy approach may be a crucial addition to current treatment. To date, the immunotherapeutic strategies for HCC have included the administration of immune stimulator cytokines, 16 gene therapy with cytokines and costimulatory molecules, 17 immunotherapy with dendritic cells loaded with specific tumor antigens, 18 and stimulation with immunogenic vaccines or antibodies. 19 Effective combinations of immunotherapy and chemotherapy or TACE remain to be explored.…”

Section: Discussionmentioning

confidence: 99%

Hapten-enhanced overall survival time in advanced hepatocellular carcinoma by ultro-minimum incision personalized intratumoral chemoimmunotherapy

Gao¹,

Peng²,

Liu³

et al. 2015

JHC

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PurposeTo compare the therapeutic effects of ultra-minimum incision personalized intratumoral chemoimmunotherapy (UMIPIC) with intratumoral chemotherapy (ITCT) in the treatment of advanced hepatocellular carcinomas and to analyze the effect of hapten as an immune booster.Materials and methodsPatients with advanced hepatocellular carcinomas were treated with UMIPIC or ITCT with the same therapeutic procedure; the UMIPIC method had a proprietary regimen including an oxidant, a cytotoxic drug, and hapten, while ITCT delivered the same drug excluding hapten. Of 339 patients in total, 119 of the UMIPIC patients (n=214) had response data and 214 had survival data, and of the ITCT patients (n=125), 61 had response data and 125 had survival data. Tumor response was assessed with a computed tomography scan 6–8 weeks after the initial treatment; the survival rate was evaluated by follow-up visits. Tumor size was classified as small (<5 cm), large (5–10 cm), or very large (>10 cm); tumor sizes with liver function categorized using Child–Pugh class (A and B) were analyzed by correlation with overall survival.ResultsThe response rates (complete response + partial response + stable disease) were 78.68% and 81.52% in the UMIPIC and ITCT groups, respectively, with no statistically significant difference; however, the median overall survival was 7 months for UMIPIC (test) and 4 months for ITCT (control), respectively (P<0.01). The 6-month and 1-year survival rates for UMIPIC and ITCT were 58.88% vs 32.3% and 30.37% vs 13.6%, respectively (P<0.01). Single and multiple UMIPIC revealed significant improvement in overall survival compared to that of ITCT. Child–Pugh class A patients had a longer duration of survival compared to Child–Pugh class B patients in UMIPIC therapy.ConclusionHapten had enhanced therapeutic effect with improvement in the survival duration in UMIPIC compared to ITCT. After reexamination, the response rate was not different due to inflammation caused by hapten. Hapten has been found to play an important role in immunotherapy to improve patient survival.

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“…Gene transfer of immunostimulatory cytokines (e.g. IL-2, IL-4, IL-6, IL-7; IL-12, INF-γ, TNF-α, GM-CSF) was shown to overcome the immune tolerance against tumors, facilitating their eradication in some cases [ 143 - 145 ] (Table 2 ). Two main approaches have been used [ 144 ]: i) direct injection of vectors expressing cytokines/chemokines/costimulatory molecules into tumor lesions, or ii) use of tumor cells/DCs transduced ex vivo with vectors expressing cytokines/costimulatory molecules.…”

Section: Gene Transfer Of Cytokines and Costimulatory Molecules Genementioning

confidence: 99%

Immunotherapy for liver tumors: present status and future prospects

et al. 2009

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Increasing evidence suggests that immune responses are involved in the control of cancer and that the immune system can be manipulated in different ways to recognize and attack tumors. Progress in immune-based strategies has opened new therapeutic avenues using a number of techniques destined to eliminate malignant cells. In the present review, we overview current knowledge on the importance, successes and difficulties of immunotherapy in liver tumors, including preclinical data available in animal models and information from clinical trials carried out during the lasts years. This review shows that new options for the treatment of advanced liver tumors are urgently needed and that there is a ground for future advances in the field.

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Cytokine gene transfer in cancer therapy

Abstract: New strategies based on gene transfer technology are employed in cancer therapy.

Cited by 14 publications

References 68 publications

Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

Effects of Long-Term Oral Administration of Arachidonic Acid and Docosahexaenoic Acid on the Immune Functions of Young Rats

Hapten-enhanced overall survival time in advanced hepatocellular carcinoma by ultro-minimum incision personalized intratumoral chemoimmunotherapy

Immunotherapy for liver tumors: present status and future prospects

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