Cytokine immunogene therapy

Abstract

<jats:p>The prognosis for patients with either a primary or metastatic brain tumor is poor. Clearly new forms of therapy to improve the long-term survival of patients with malignant brain tumors are urgently needed. The authors are in the process of developing a new and novel form of treatment for primary and metastatic brain tumors in which they use genes involved in growth repression. In particular most tumors fail to induce an antitumor immune response strong enough to kill the tumor. Under appropriate circumstances, however, immunity can be produced in unique structures on the tumor cells known as antigens. To prepare the vaccine, genes are transferred into a fibroblast cell line that causes the cell to produce cytokines, the potent proteins known to stimulate the immune system. These cells are subsequently injected into the tumor bed, resulting in the development of an antitumor immune response. In experiments described in this manuscript, the authors have investigated a number of ways of augmenting the immune response by administering this type of cellular vaccine. They found that mice with a primary intracerebral glioma, melanoma, or breast cancer treated with this allogeneic cytokine-secreting vaccine survived significantly longer than untreated mice. Additionally the vaccine was found to stimulate a systemic antitumor immune response, as shown by immunocyto-toxic studies, histopathological examination, and delayed immune memory responses. In summary, these results indicate that immunogene therapy is a promising new targeted therapy for the treatment of intracerebral malignant tumors.</jats:p>

Novel Immunotherapeutics for Treatment of Glioblastoma: The Last Decade of Research

“…Treatments can include transferring genes for inflammatory proteins to tumor cells, inhibition of immunosuppressing tumor genes, or transferring proinflammatory and tumor antigen genes to professional antigen presenting cells. Previous clinical trials have focused on conditional cytotoxicity and oncolytic viruses, which may induce a secondary immune response by generating foreign antigens and producing a proinflammatory immune beacon in tumor cells [42][43]. Several clinical trials using adenovirus, herpes simplex virus, replicating retroviruses have been conducted with preliminary results demonstrating survival benefit [16].…”

Novel Immunotherapeutics for the Treatment of Glioblastoma: The Last Decade of Research

“…Treatments can include transferring genes for inflammatory proteins to tumor cells, inhibition of immunosuppressing tumor genes, or transferring proinflammatory and tumor antigen genes to professional antigen presenting cells. Previous clinical trials have focused on conditional cytotoxicity and oncolytic viruses, which may induce a secondary immune response by generating foreign antigens and producing a pro-inflammatory immune beacon in tumor cells [ 42 - 43 ]. Several clinical trials using adenovirus, herpes simplex virus, replicating retroviruses have been conducted with preliminary results demonstrating survival benefit [ 16 ].…”

Immunotherapy and Therapeutic antibodies

“…Stimulation of a systemic antitumor immune response was proved by immunocytotoxic studies, histopathological examination, and delayed immune memory responses. Thus, immunogene therapy is a promising new targeted therapy for the treatment of intracerebral malignant tumors [44]. The Preoperative immunotherapy with interleukin-2 may contribute to massive stromal infiltration of immune cells in pancreatic adenocarcinoma.…”