Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine malignant mesothelioma

Our plain-English summary of Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine malignant mesothelioma, by C.C. Leong, J.V. Marley, S. Loh, et al (International Journal of Cancer, 1997).

The study

• Authors: C.C. Leong, J.V. Marley, S. Loh, N. Milech, B.W. Robinson, M.J. Garlepp
• Journal: International Journal of Cancer
• Published: 1997;71(3):476-82
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Transfection of the genes encoding the co-stimulatory molecules B7-1 and B7-2 has enhanced the development of immunity to a variety of experimental tumors, although most of these were inherently immunogenic. We have determined the effect of expression of these genes on the induction of immunity to 2 non-immunogenic murine malignant mesothelioma (MM) cell lines (AC29 and AB1). We had previously shown that B7-1 transfection into AC29 delayed but did not prevent tumor development by certain of the transfectant clones. Here we demonstrate that over-expression of B7-1 can inhibit tumor development by certain AB1-B7-1 clones, that inhibition of transfectant growth is dependent on CD4+ and CD8+ T cells and that mice that reject some of these transfectant clones are capable of rejecting subsequent inocula of the parental cell line, AB1. The transfectant clones can generate tumor-specific cytotoxic T cells. By contrast, expression of B7-2 in several clones derived from either AB1 or AC29 had no significant effect on the development of tumors in vivo. Our data are consistent with data from other systems that show differences in the effect of modification by B7-1 or B7-2 on the modulation of anti-tumor immune responses. They demonstrate that such modifications can induce protective immunity against an MM cell line but confirm the intra- and inter-tumoral heterogeneity in the effect of genetic modification on the induction of immunity. Our observations are relevant to human MM because these cell lines have been derived from asbestos-induced tumors and share many properties with human cell lines of the same histological type.

In plain English

In this mouse experiment, the authors used two mouse malignant mesothelioma cell lines, AB1 and AC29. These lines came from tumors induced by injecting crocidolite asbestos into mice. The authors called both lines non-immunogenic, which they defined as irradiated cells failing to protect against later live cells and unmodified cells not inducing cytotoxic (cell-killing) T cells. In this study, injecting irradiated AB1 cells did not protect mice against later live AB1 cells. The authors inserted genes for two immune 'co-stimulatory' molecules, B7-1 and B7-2, into the cells and injected the altered cells under the skin. With four B7-1 AB1 clones, some mice given each clone except one (AB1.7–B7-1) did not develop tumors. When those tumor-free mice were later given the original AB1 cells, tumors were either delayed or did not grow. Mice depleted of CD4 or CD8 T cells developed tumors faster. Cells carrying B7-2, from both lines, grew like the original cells. The authors concluded that gene modification could induce protective immunity against an apparently non-immunogenic mesothelioma cell line. They called this protection 'somewhat brittle' and noted variation between and within tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: mouse mesothelioma cell lines that the authors describe as non-immunogenic were genetically modified (transfected) with B7-1 or B7-2 genes and injected into mice. The authors' working definition of non-immunogenic is that irradiated tumor cells fail to induce protective immunity against later live parental cells, and the unmodified cell line does not induce cytotoxic T cells.
• Who was studied: Two murine malignant mesothelioma cell lines, AB1 (from a BALB/c mouse) and AC29 (from a CBA mouse), tested in female BALB/c or CBA mice aged 6 to 8 weeks, in Western Australia; 10 mice per group in the B7-2 experiments shown
• Exposure: The tumors behind the cell lines were originally induced with crocidolite asbestos. The experimental intervention was transfection of the cells with genes for the co-stimulatory molecules B7-1 or B7-2, followed by injection of the modified cells into mice.
• Main results:
  • Immunisation with irradiated parental AB1 cells did not induce protective immunity.
  • Of four AB1 clones carrying B7-1, each except AB1.7–B7-1 failed to form tumors in a proportion of the mice inoculated.
  • Mice that had rejected an AB1-B7-1 clone and were rechallenged with parental AB1 cells showed either delayed tumor outgrowth or no tumor growth.
  • Mice depleted of CD4 or CD8 T cells developed tumors from clone AB1.14–B7-1 more quickly than undepleted mice. Of the undepleted mice, 2 of 5 did not form tumors.
  • B7-2 transfectant clones from both AB1 and AC29 grew like the parental cell lines. In the experiments shown, all 10 mice per group developed tumors.
  • Inoculation of clone AB1.14B7-1 generated immune cells that killed both transfectant clones and parental AB1 cells. Inoculation of AB1–B7-2 transfectants did not generate this activity after 8 or 16 days.
• The authors' conclusion: The authors concluded that gene transfection could induce protective immunity against an apparently non-immunogenic mesothelioma cell line, and that mesothelioma cells express antigens that T cells can recognise.
• Limitations the authors state:
  • The protection was inconsistent: not all mice rejected the transfectants, and some that did were not protected against later challenge.
  • Responses varied between and within mesothelioma cell lines, which the authors described as a major obstacle to using genetic modification.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma.

Related studies

• Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation — A.J. Currie, A. Prosser, et al. (2009)
• Transfection of a manganese-containing superoxide dismutase gene into hamster tracheal epithelial cells ameliorates asbestos-mediated cytotoxicity — B.T. Mossman, P. Surinrut, et al. (1996)
• Efficacy of repeated adenoviral suicide gene therapy in a localized murine tumor model — E.S. Lambright, S.D. Force, et al. (2000)
• An analysis of the relationship between gamma delta T cell receptor V gene usage and non-major histocompatibility complex-restricted cytotoxicity — N. Mavaddat, B.W. Robinson, et al. (1993)
• Identification of cancer stem cell markers in human malignant mesothelioma cells — F.I. Ghani, H. Yamazaki, et al. (2011)
• Identification of carcinogens by measurement of cell-mediated immunity. III. Immunity to asbestos-induced rat peritoneal mesothelioma — D.A. Cole, R.H. Stevens, et al. (1982)

Browse more research in International Journal of Cancer, or return to medical research.