An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

Zoeten, Edwin F. de; Marković, Dubravka; Cohen, Edward P.

doi:10.1038/sj.gt.3301765

Cited by 9 publications

(10 citation statements)

References 42 publications

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“…Allogeneic MHC-determinants are strong immune adjuvants. 20 To further augment their immunogenic properties, the cytokine-secreting fibroblasts used as DNA recipients were subsequently modified to express H-2K b -determinants. A plasmid, pBR327H-2K b , was used for this purpose.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer

et al. 2005

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Prior studies have revealed the immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA from breast cancer cells into a highly immunogenic cell line. The rationale for this type of vaccine is that genes specifying an array of weakly immunogenic, unique tumor antigens associated with the malignant cells will be expressed in a highly immunogenic form by the transfected cells. Here, the immunotherapeutic properties of a vaccine prepared by transfection of mouse fibroblasts with DNA from a breast carcinoma (SB-5b) that arose spontaneously in a C3H/He mouse (H-2K b ) were tested in mice with intracerebral breast cancer. To augment their nonspecific immunogenic properties, before DNA transfer, the fibroblasts (of C3H/He mouse origin) were modified to express allogeneic MHC class I H-2K b -determinants and to secrete IL-2, IL-18 or GM-CSF. The results indicate that C3H/He mice injected intracerebrally (i.c.) with the breast cancer cells and syngeneic/allogeneic-transfected fibroblasts modified to secrete IL-2 survived significantly longer (Po.005) than mice in various control groups, including mice injected i.c. with the breast cancer cells alone. The immunotherapeutic properties of transfected fibroblasts modified to secrete IL-18 or GM-CSF were less efficacious. The results of two independent in vitro cytotoxicity assays indicate that systemic cellular antitumor immunity was generated in mice injected i.c. with the transfected cells, and the immunity was mediated predominantly by CD8 þ T cells.

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Section: Resultsmentioning

confidence: 99%

Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer

et al. 2005

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“…Immunization of tumor-bearing mice with the DNAbased vaccine resulted in the induction of cell mediated immunity directed toward the type of tumor from which the DNA was obtained, and prolongation of survival, consistent with the expression of an array of TAA by the transfected cells. This was the case for mice with melanoma, squamous cell carcinoma and in mice with breast cancer [Chopra et al, 2006;deZoeten et al, 2002;Lichtor et al, 2008]. Multiple undefined genes specifying TAA that characterize the malignant cell population were expressed by cells that took up DNA from the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of both syngeneic and allogeneic MHC-determinants by the DNA recipient cells is important in order to obtain an optimum anti-tumor response [deZoeten et al, 2002]. The syngeneic determinants provide a restriction element for direct presentation of TAAs to CTLs of the host.…”

Section: 5mentioning

confidence: 99%

Development of a DNA-Based Vaccine for Treatment of an Intracerebral Tumor

Lichtor¹,

Glick²

2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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“…26 Preparation of cDNA libraries from SB5b breast cancer and B16F1 melanoma cells Guanidine isothiocyanate was used to recover total RNA from SB5b breast or B16F1 melanoma cells (used as a specificity control) from in vitro culture. The mRNA, derived from 1 Â 10 7 cells, was isolated using an mRNA isolation system (Promega, Madison, WI).…”

Section: Modification Of Lm Fibroblasts To Secrete Il-2mentioning

confidence: 99%

Immunity to breast cancer in mice immunized with fibroblasts transfected with a cDNA expression library derived from small numbers of breast cancer cells

Kim

Cohen

2005

Cancer Gene Ther

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Immunotherapy of breast cancer at an early stage of the disease increases the likelihood of success. Here, in a mouse model, we report a new strategy that enables vaccines to be prepared from microgram amounts of tumor tissue. The vaccine is prepared by transfer of a cDNA expression library from relatively small numbers of breast cancer cells into a highly immunogenic cell line, where genes specifying TAA are expressed. As the transferred DNA is integrated and replicated as the recipient cells divide, the number of vaccine cells can be conveniently expanded for repeated immunizations. A cDNA expression library prepared from a breast cancer that arose spontaneously in a C3H/He mouse (H-2 k ) was transferred into a mouse fibroblast cell line derived from C3H/He mice. To augment their nonspecific immunogenic properties, the fibroblasts were genetically modified before DNA transfer to secrete IL-2 and to express allogeneic MHC class I H-2K b -determinants. C3H/He mice, highly susceptible to growth of the breast cancer cells, were immunized with the cDNA-transfected cells. Robust breast cancer-specific CD8 þ T-cell-mediated immunity was generated in the mice, raising the possibility that an analogous treatment strategy could be used to treat breast cancer patients at an early stage of the disease.

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An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants

Abstract: Most neoplasms do not induce antitumor immune responses

Cited by 9 publications

References 42 publications

Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer

Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer

Development of a DNA-Based Vaccine for Treatment of an Intracerebral Tumor

Immunity to breast cancer in mice immunized with fibroblasts transfected with a cDNA expression library derived from small numbers of breast cancer cells

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