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Melanoma cells expressing membrane‐anchored IL‐2 and IL‐12 induce effective antitumor immunity in the presence or absence of B7‐1 costimulation
Author(s) -
Shashidharamurthy Rangaiah,
Panchanathan Ravichandran,
Fiske Erik D,
Tien Linda,
Selvaraj Periasamy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1078.21
Subject(s) - melanoma , immune system , transfection , clone (java method) , cancer research , immunology , immunotherapy , biology , in vivo , cell culture , dna , genetics , microbiology and biotechnology
Systemic and local administration of cytokines has been used as a strategy to induce an antitumor immune response to enhance the antitumor effects of many cancer vaccines. This study investigates the antitumor effects of certain cytokines and costimulatory molecules expressed on tumor cell surface as a glycolipid (GPI)‐anchored form using a murine melanoma (S91 clone M3) model. Stable transfectants of S91 cells expressing immunostimulatory molecules, such as B7‐1, IL‐2, and IL‐12, alone and in combinations were established. The transfected cells induced the proliferation of activated T cells, indicating that membrane‐expressed GPI‐anchored cytokines can stimulate immune cells directly. To determine the in vivo efficacy of these immunostimulatory molecules, groups of mice were challenged with transfected cells and no tumor growth was observed. After 56 days of observation, the immunized mice were re‐challenged with wild‐type S91 melanoma cells. The mice immunized with transfected cells did not develop tumors whereas the unimmunized control mice developed tumors. In summary, our results show that the GPI‐anchored cytokines alone or in combination with B7‐1 can augment antitumor immune response, which suggest that the combination of immunostimulatory molecules expressed on melanoma cells can be used as a vaccine against melanoma.