Regulation of human cytolytic lymphocyte responses by interleukin-12

Gately, Maurice K.; Wolitzky, A G; Quinn, P M; Chizzonite, R

doi:10.1016/0008-8749(92)90011-d

Cited by 304 publications

(158 citation statements)

References 32 publications

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“…1 In addition to the stimulatory effect on NK cells, bioactive IL-12 can activate cytotoxic T lymphocytes (CTLs). [2][3][4] Induction of cytokines, such as interferon-g (IFN-g), IFN-inducible protein-10 (IP-10), and monokine induced by IFN-g (MIG), has also been implicated as a mechanism of antitumor activity of IL-12. 5,6 These diverse effects make IL-12 an attractive candidate as a therapeutic agent for cancer treatment.…”

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confidence: 99%

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

et al. 2003

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Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising anticancer therapy. Vectors are currently being developed to achieve safe and effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric acid] (PDBA) is a novel gene carrier that was recently described. The goal of this study was to use this gene delivery system for treatment of solid tumors. To determine the optimal conditions for transfection, established B16F10-melanomas in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid luciferase (pLuc) complex. We determined that the optimal complex composition was 50 mg/ml pLuc and 150 mg/ml PDBA. High levels of IL-12 protein were expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12) complex, whereas serum levels of IL-12 in treated mice were below the limits of detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor growth in comparison with the controls (Po.001). Moreover, both natural killer and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12-treated mice were increased substantially in comparison with those of controls (Po.05). These results suggest that PDBA-mediated IL-12 gene therapy is a potential strategy for treatment of patients with solid tumors.

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confidence: 99%

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

et al. 2003

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“…Although the mechanisms by which fractalkine exerts its antitumor activity on osteosarcoma lung lesions have not been identified yet, we can suppose that innate immunity (via NK cells) and adaptive immunity (via CD8 þ T cells and/or dendritic cell) are likely to play a major role in mediating tumor regression of osteosarcoma lung metastasis as reported in colon carcinoma and in many other solid tumors development. [8][9][10][11]13,30,31 In addition to reinforcing this assumption, IL-12, which notably activates NK cells and facilitates the induction of cytotoxic and T helper type 1 T cells, [32][33][34][35] was found to inhibit the development of osteosarcoma lung metastases.…”

Section: Discussionmentioning

confidence: 93%

Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

et al. 2011

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The lung is one target organ to which solid tumors frequently metastasize. Given the systemic adverse effects of currently available treatments, developing effective strategies of drug/gene delivery directly to the lungs is therefore needed. Aerosol delivery is a noninvasive gene transfer approach to target the airways. Here, we sought to evaluate the potential to deliver a fractalkine (FKN)-encoding plasmid formulated with the tetrafunctional amphiphilic block copolymer 704 through aerosolization in two models of pulmonary metastases. FKN is a chemokine recently described as a good candidate to stimulate a strong antitumor immune response in various forms of cancers. Here, we have assessed the effect of single and repeated aerosolizations of FKN-encoding plasmid formulated with 704 on the development of experimental lung metastases of mouse colon carcinoma and osteosarcoma. For this purpose, we have designed FKN-Fc sequences encoding an optimized version of the chemokine. Repeated intratracheal administrations of 704/FKN-Fc markedly inhibited growth of experimental lung metastases of CT-26 and K7M2 cells. Our results showed that tetrafunctional amphiphilic block copolymer 704 is a highly efficient synthetic vector for mediating local and safe gene transfer into the lung. In addition, FKN-Fc gene therapy of pulmonary nodules may provide a promising immunotherapeutic approach.

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“…This has allowed a study of the effect of immunomodulatory agents on the generation of autologous, anti-melanoma CTL. IL-12 has been shown to facilitate both non-specific LAK and specific CTL responses against human allogeneic tumour cells [20,38] and other targets [36]. We therefore optimized CTL generation by the addition of hydrocortisone [48], which decreased the generation of non-specific LAK and NK cells during in vitro, allogeneic PBL stimulation (data not shown).…”

Section: Il-12 Stimulates the Generation Of Patient Anti-melanoma Ctlmentioning

confidence: 99%

“…IL-12 is produced by macrophages and B lymphocytes and has been shown to have multiple effects on T cells and natural killer (NK) cells, including induction of the production of IFN-and tumour necrosis factor (TNF) by resting and activated T and NK cells [20,34] and enhancement of cytotoxic activity of T lymphocytes and NK cells [19,[35][36][37][38]. IL-12 is also a central regulator of the cell-mediated immune response because of its actions on the development, proliferation, and activity of Th1 lymphocytes [20,39,40].…”

Section: Introductionmentioning

confidence: 99%

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

Wit

Flemming

Harris

et al. 1996

Clinical and Experimental Immunology

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SUMMARYRecent studies have demonstrated that rodent tumour cells engineered to secrete a variety of cytokines, or to express foreign antigens, MHC molecules or co-stimulatory molecules, are rejected by syngeneic animals. These observations have led to the initiation of a number of clinical trials using genetically modified tumour cells, to attempt to stimulate a patient anti-tumour immune response. In this study, a protocol has been developed to test in vitro the specific cytotoxic anti-tumour response generated from melanoma patient lymphocytes. The results showed that IL-12 in combination with IL-2 enhanced the autologous anti-melanoma CTL response, whereas B7.1 antigen expression on tumour cells did not increase anti-melanoma CTL generation. This method could be used to design more appropriate genetically modified tumour vaccines.

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Regulation of human cytolytic lymphocyte responses by interleukin-12

Cited by 304 publications

References 32 publications

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

Effect of fractalkine-Fc delivery in experimental lung metastasis using DNA/704 nanospheres

IL-12 stimulation but not B7 expression increases melanoma killing by patient cytotoxic T lymphocytes (CTL)

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