The mechanism of exogenous B7.1‐enhanced IL‐12‐mediated complete regression of tumors by a single electroporation delivery

Liu, Jianguo; Xia, Xueqing; Torrero, Marina N.; Barrett, Robin; Shillitoe, Edward J.; Li, Shulin

doi:10.1002/ijc.22100

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…The effect was more pronounced in SCVII tumors with 80% tumor cures. The cured mice also developed antitumor immunity [97]. A high complete response rate (100%) was also obtained in CT-26 tumors treated with a combination of IL-12 and IL-27 electrogene therapy.…”

Section: Il-12 Electrogene Therapy In Combination With Other Therapiesmentioning

confidence: 87%

Cancer Electrogene Therapy with Interleukin-12

Čemažar¹,

Jarm²,

Serša

2010

CGT

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Electrogene therapy combines administration of plasmid DNA into tissue followed by local application of electric pulses. In electrogene therapy with interleukin-12 (IL-12), different routes of administration, different doses of plasmid DNA and different protocols for delivery of electric pulses were evaluated in numerous preclinical studies. Antitumor effectiveness was tested in different types of primary tumors, distantly growing tumors and induced metastases. Intratumoral IL-12 electrogene therapy has been proved to be very effective in local tumor control, having also a systemic effect. Intramuscular and peritumoral IL-12 electrogene therapy had also a pronounced systemic effect and when combined with other treatment strategies resulted in tumor cures. Antitumor effectiveness of IL-12 electrogene therapy is due to the induction of adaptive immunity and innate resistance and anti-angiogenic action. Translation of preclinical studies into clinical trials in human and veterinary oncology has started with encouraging results that would hopefully lead to further investigation of this therapy, also in combination with other cancer treatment modalities.

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Section: Il-12 Electrogene Therapy In Combination With Other Therapiesmentioning

confidence: 87%

Cancer Electrogene Therapy with Interleukin-12

Čemažar¹,

Jarm²,

Serša

2010

CGT

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“…A limited number of these studies have demonstrated long-term, complete tumor regression, including studies delivering plasmids encoding interleukin (IL)-12 (2–6), interferon (IFN) α (7;8), IL-15 (9), and IL-21 (10) as single agents. Complete tumor regression was observed after delivery of combinations of plasmids encoding IL-6 and IL-15 (11), GM-CSF and B7.1 (12), or IL-12 and B7.1 (13). Intratumor electroporation of a plasmid encoding the human IL-12 cDNAs for melanomas has been successful therapeutically in a Phase I clinical trial (14).…”

Section: Introductionmentioning

confidence: 99%

Plasmid injection and application of electric pulses alter endogenous mRNA and protein expression in B16.F10 mouse melanomas

et al. 2010

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The application of electric pulses to tissues causes cell membrane destabilization, allowing exogenous molecules to enter the cells. This delivery technique can be used for plasmid gene therapy. Reporter gene expression after plasmid delivery with eight representative published protocols was compared in B16.F10 mouse melanoma tumors. This expression varied significantly based on the pulse parameters utilized for delivery. To observe the possible influence of plasmid injection and/or pulse application on endogenous gene expression, levels of stress related mRNAs four and 24 hours after delivery were determined by PCR array. Increases in mRNA levels for several inflammatory chemokines and cytokines were observed in response to plasmid injection, electric pulses alone, or the combination. This upregulation was confirmed by individual real-time reverse transcription TaqMan PCR assays. Proteins were extracted at the same time points from identically treated tumors and inflammatory protein levels were assayed by ELISA and by a custom multiplex bead array. Increases in inflammatory protein levels generally paralleled mRNA levels. Some differences were observed, which may have been due to differing expression kinetics. The observed upregulated expression of these cytokines and chemokines may aid or inhibit the therapeutic effectiveness of immune-based cancer gene therapies.

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“…Mouse TAP1 and TAP2 cDNA was inserted into the vectors pcDNA3.1/His and pUB6/V5-His (Invitrogen Corporation, Carlsbad, CA) as described previously [36]. A B7.1-vector [37] was provided by Dr. Li, S (Louisiana State University, Baton Rouge, LA). B7.1 cDNA was isolated and inserted into a pUB6/V5-His vector (Invitrogen Corporation).…”

Section: Methodsmentioning

confidence: 99%

Effect of B7.1 Costimulation on T-Cell Based Immunity against TAP-Negative Cancer Can Be Facilitated by TAP1 Expression

Knight

Odaka

et al. 2009

PLoS ONE

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Tumors deficient in expression of the transporter associated with antigen processing (TAP) usually fail to induce T-cell-mediated immunity and are resistant to T-cell lysis. However, we have found that introduction of the B7.1 gene into TAP-negative (TAP−) or TAP1-transfected (TAP1+) murine lung carcinoma CMT.64 cells can augment the capacity of the cells to induce a protective immune response against wild-type tumor cells. Differences in the strength of the protective immune responses were observed between TAP− and TAP1+ B7.1 expressing CMT.64 cells depending on the doses of γ-irradiated cell immunization. While mice immunized with either high or low dose of B7.1-expressing TAP1+ cells rejected TAP− tumors, only high dose immunization with B7.1-expressing TAP− cells resulted in tumor rejection. The induced protective immunity was T-cell dependent as demonstrated by dramatically reduced antitumor immunity in mice depleted of CD8 or CD4 cells. Augmentation of T-cell mediated immune response against TAP− tumor cells was also observed in a virally infected tumor cell system. When mice were immunized with a high dose of γ-irradiated CMT.64 cells infected with vaccinia viruses carrying B7.1 and/or TAP1 genes, we found that the cells co-expressing B7.1 and TAP1, but not those expressing B7.1 alone, induced protective immunity against CMT.64 cells. In addition, inoculation with live tumor cells transfected with several different gene(s) revealed that only B7.1- and TAP1-coexpressing tumor cells significantly decreased tumorigenicity. These results indicate that B7.1-provoked antitumor immunity against TAP− cancer is facilitated by TAP1-expression, and thus both genes should be considered for cancer therapy in the future.

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The mechanism of exogenous B7.1‐enhanced IL‐12‐mediated complete regression of tumors by a single electroporation delivery

Cited by 10 publications

References 39 publications

Cancer Electrogene Therapy with Interleukin-12

Cancer Electrogene Therapy with Interleukin-12

Plasmid injection and application of electric pulses alter endogenous mRNA and protein expression in B16.F10 mouse melanomas

Effect of B7.1 Costimulation on T-Cell Based Immunity against TAP-Negative Cancer Can Be Facilitated by TAP1 Expression

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