Retrovirus-mediated IL-4 gene therapy in spontaneous adenocarcinomas from MMTV-neu transgenic mice

Abstract

Gene therapy approaches to the treatment of experimental mice. The size of IL-4 inoculated tumors on the right side cancer are usually based on established neoplastic cell was significantly smaller than that of controlateral lines which are manipulated in vitro and subsequently untreated tumors, suggesting a local effect of IL-4. In transplanted in host animals. However, the relevance of addition, the non-injected tumors on the left side of treated these artificial models to the biology and therapy of human animals were significantly smaller than those arising in tumors is uncertain. We have previously validated an control transgenic mice, suggesting that IL-4 can also experimental model based on MMTV-neu transgenic mice inhibit tumor growth systemically. These findings suggest in which breast tumors arise spontaneously in 100% of anithat IL-4 gene transfer can significantly reduce the growth mals and have many features in common with their human rate of spontaneously arising breast tumors and that counterpart, including the involvement of the neu oncoimmune-based gene therapy could efficiently complement gene and the ability to metastatize. In this article we report other approaches based on different mechanisms, such as the effect of intratumoral, retrovirus-mediated, IL-4 suicide gene transfer or antisense technology. expression on the growth of breast tumors arising in these

Combined antiestrogen, antiangiogenic and anti-invasion therapy inhibits primary and metastatic tumor growth in the MMTVneu model of breast cancer

“…5,6 We have therefore pioneered the use of transgenic mice as models for evaluation of new gene therapy strategies. [6][7][8][9][10][11][12] We have extensively used a transgenic mouse model (MMTVneu) of breast carcinoma, which has many similarities with its human counterpart. Briefly, breast tumors in MMTVneu mice occur spontaneously, overexpress the neu oncogene, escape the immune system, grow in situ and adapt to the microenvironment, recruit vessels, invade the tissues, penetrate the vasculature and give rise to distant metastases.…”

Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice

“…15 The effect of therapy with human and murine genes on local tumor growth inhibition was evaluated by comparing the tumor weight in all the treatment groups, as done in our previous work. [9][10][11][12][13] While in 5-month-old control animal tumors reached the size of about 1 g, in all the treated groups we observed an inhibition of tumor growth with all the constructs. The reduction of tumor weight was about 40% in the TIMP2-treated group, 50% in the MMTVang and BSHend and about 65% in the BSHang-treated groups compared with the control one (see Figure 2).…”

“…Therefore, we have extensively validated a transgenic mouse model of breast carcinoma which has many similarities with its human counterpart, including the ability to give rise to distant metastases, allowing us to investigate the efficacy of novel gene therapy-based approaches on metastatic growth. [9][10][11][12][13] As previously shown, in this model, based on MMTV-neu transgenic mice, breast tumors grow very reproducibly in 100% of the transgenic females, arise relatively slowly in an immunocompetent host and involve the neu oncogene, which is known to play a role in human breast cancer. In addition, these tumors give rise to distant metastases in the 4th or 5th month of age, which are easily detected by histopathological examination.…”

Combined effects on tumor growth and metastasis by anti-estrogenic and antiangiogenic therapies in MMTV-neu mice

“…6,7,10 We have tested various gene therapy approaches to the treatment of breast cancer in this model, including the suicide, antisense and immune stimulating strategies. [10][11][12][13] We have shown that the results obtained in this model are more representative of what happens in the human pathology than those obtained with transplantable cultured tumoral cells injected in the immunocompromised host. More recently, by using this model, we have been able to show that liposome-mediated angiostatin gene delivery significantly reduces local tumor growth and abolishes its metastatic spread to lungs.…”