Interleukin-2 gene therapy of surgical minimal residual tumour disease

Vlk, V.; Rössner, Pavel; Indrová, M; Bubenı́k, Jan; Sobota, V

doi:10.1002/(sici)1097-0215(19980330)76:1<115::aid-ijc18>3.0.co;2-b

Cited by 11 publications

(3 citation statements)

References 16 publications

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“…It corresponds with our previous results using a murine model that the treatment before surgery with irradiated IL-2 producing tumor cells used as a cellular vaccine was without effect. 30 These facts show that proper timing of DC vaccine administration (or immunotherapy in general) and surgery can be crucial for the final therapeutic output. Notably, in humans, possible clinical benefit has been suggested for adjuvant immunotherapy using autologous DC loaded with autologous tumor lysate after revision in patients with relapsed glioblastoma multiforme.…”

Section: Discussionmentioning

confidence: 99%

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Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice

et al. 2017

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Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)-inactivated tumor cells have recently been shown to be a promising tool for prostate cancer chemoimmunotherapy. In this study, DC-based vaccines, both pulsed and unpulsed, were as effective as docetaxel (DTX) in reducing prostate tumors in the orthotopic transgenic adenocarcinoma of the mouse prostate (TRAMP) model. However, we did not observe any additive or synergic effects of chemoimmunotherapy on the tumor growth, while only the combination of DTX and pulsed dendritic cells resulted in significantly lower proliferation detected by Ki67 staining in histological samples. The DC-based vaccine pulsed with HHP-treated tumor cells was also combined with another type of cytostatic, cyclophosphamide, with similar results. In another clinically relevant setting, minimal residual tumor disease after surgery, administration of DC-based vaccines after the surgery of poorly immunogenic transplanted TRAMP-C2, as well as in immunogenic TC-1 tumors, reduced the growth of tumor recurrences. To identify the effector cell populations after DC vaccine application, mice were twice immunized with both pulsed and unpulsed DC vaccine, and the cytotoxicity of the spleen cells populations was tested. The effector cell subpopulations were defined as CD4 and NK1.1, which suggests rather unspecific therapeutic effects of the DC-based vaccines in our settings. Taken together, our data demonstrate that DC-based vaccines represent a rational tool for the treatment of human prostate cancer.

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Section: Discussionmentioning

confidence: 99%

“…anesthesia, leaving no macroscopically visible tumor residuum. 30 The hypothetical microscopic tumor residua after surgery were designated as surgical minimal residual tumor disease. Mice were randomly divided into 3 experimental groups.…”

Section: Treatment Of Surgical Minimal Residual Tumor Diseasementioning

confidence: 99%

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice

et al. 2017

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“…anaesthesia, leaving no macroscopically visible tumour residuum (34). The hypothetical microscopic tumour residua after surgery were designated as surgical minimal residual tumour disease.…”

Section: Il-12 Gene Therapy Of Mk16 Residual Disease After Surgerymentioning

confidence: 99%

Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine

Reiniš¹

2011

Oncol Rep

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Abstract. genetically modified tumour cells producing cytokines such as interleukin 12 (Il-12) are potent activators of the antitumour immune responses and represent a promising therapeutic modality when combined with chemotherapy. the objective of this study was to examine whether Il-12-producing cellular vaccines can augment chemotherapy of human papilloma virus (HpV) 16-associated murine tumours with the cytostatic agent gemcitabine (geM). We found that peritumoral administration of Il-12-producing tumour vaccines enhanced the effect of cytoreductive therapy with geM both in non-metastasizing murine carcinoma tc-1 and in metastasizing murine carcinoma MK16. the percentage of mice with MK16 metastases and the number of lung metastatic nodules was substantially decreased. In another clinically relevant setting, surgical minimal residual tumour disease, the administration of Il-12-producing tumour vaccine and geM after the MK16 tumour surgery reduced the percentage of mice with tumour recurrences; similarly, the percentage of metastasis-bearing mice and the number of metastatic nodules was decreased. tumour inhibitory effects exerted by geM plus Il-12 were associated with high production of interferon-γ (IFnγ) by splenocytes. our results suggest that the Il-12-producing vaccine can enhance the effect of geM chemotherapy in some HpV16-associated murine tumour models.

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Cancer vaccines: Clinical development challenges and proposed regulatory approaches for patient access to promising treatments

Stebbing

Wood

Atkins

et al. 2008

Cancer

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The complement pathway plays a central role in innate immunity, and also functions as a regulator of the overall immune response. We evaluated whether polymorphisms in complement genes are associated with event‐free survival (EFS) in follicular lymphoma (FL) and diffuse large B‐cell (DLBCL) lymphoma. We genotyped 167 single nucleotide polymorphisms (SNPs) from 30 complement pathway genes in a prospective cohort study of newly diagnosed FL (N = 107) and DLBCL (N = 82) patients enrolled at the Mayo Clinic from 2002 to 2005. Cox regression was used to estimate hazard ratios (HRs) for individual SNPs with EFS, adjusting for FLIPI or IPI and treatment. For gene‐level analyses, we used a principal components based gene‐level test. In gene‐level analyses for FL EFS, CFH (P = 0.009), CD55 (P = 0.006), CFHR5 (P = 0.01), C9 (P = 0.02), CFHR1 (P = 0.03), and CD46 (P = 0.03) were significant at P < 0.05, and these genes remained noteworthy after accounting for multiple testing (q < 0.15). SNPs in CFH, CFHR1, and CFHR5 showed stronger associations among patients receiving any rituximab, while SNPs from CD55 and CD46 showed stronger associations among patients who were observed. For DLBCL, only CLU (P = 0.001) and C7 (P = 0.03) were associated with EFS, but did not remain noteworthy after accounting for multiple testing (q>0.15). Genes from the regulators of complement activation (CFH, CD55, CFHR1, CFHR5, CD46) at 1q32–q32.1, along with C9, were associated with FL EFS after adjusting for clinical variables, and if replicated, these findings add further support for the role of host innate immunity in FL prognosis. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

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Interleukin-2 gene therapy of surgical minimal residual tumour disease

Cited by 11 publications

References 16 publications

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure inhibit prostate tumor growth in TRAMP mice

Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine

Cancer vaccines: Clinical development challenges and proposed regulatory approaches for patient access to promising treatments

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