In vivo tumor co-transfection with superantigen and CD80 induces systemic immunity without tolerance and prolongs survival in mice with hepatocellular carcinoma

Abstract

Background. Since transfection of established tumors with immunostimulatory genes can elicit antitumor immunity, we treat mouse HCC with in vivo transfection of superantigen SEA and/or costimulatory molecule CD80 and evaluated the safety and efficacy.Methods. Mice with HCC were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin A and/or CD80. Then the mice were evaluated for tumor regression, systemic immunologic responses, survival times and treatment-associated toxicity.Results. Of all treated mice, the overall response rates (complete or partial remission) for SEA, CD80 and SEA/CD80 treated mice in this study were 65%, 60% and 75% separately, and were significantly higher than that of untreated mice. Most of the treat mice completed the therapy without any significant reaction. CTL activity increased with time of treatment and correlated temporally with an objective tumor response. Also our results indicated that local intratumoral expression of SEA did not lead to detectable deletion or anergy of SEA-reactive spleen T cells. Survival times for hepatoma mice in this study treated by intratumoral injection of SEA, CD80 and SEA/CD80 were prolonged significantly (p < 0.01) compared with the control mice.

Triple expression of B7-1, B7-2 and 4-1BBL enhanced antitumor immune response against mouse H22 hepatocellular carcinoma

“…Accumulating data have revealed that costimulatory molecules are often downregulated or lost in HCC cells (Fujiwara et al 2004;Tatsumi et al 1997). Previous investigators have shown that the genetic modiWcation of HCC cells to express elevated levels of costimulatory molecules can elicit protective and sometimes curative immunity against unmodiWed HCC tumor cells (Li et al 2004). In addition, the expression of many costimulatory molecules in a tumor cell seems to be more eYcient than the expression of single molecule in eliciting tumor-speciWc T-cell immunity (Disis et al 2009).…”

Identification of HLA-A2-restricted CTL epitope encoded by the MAGE-n gene of human hepatocellular carcinoma

“…8,9 Our lab has made an effort to establish effective immunotherapy in recent few years. [10][11][12] In view of the fact that HLA-A2 is positive in 53.5% of HCC patients in China population, 13 it is valuable to investigate whether the epitope of MAGE-n antigen presented by HLA-A2 could induce primary, peptide-specific CTL against HCC cells.…”

Polyethylenimine-mediated in vivo gene transfer of a transmembrane superantigen fusion construct inhibits B16 murine melanoma growth

“…[18][19][20][21] Another strategy consists in direct transfection of a SAg into the tumor, which elicits local and systemic immune responses and leads to tumor regression without systemic toxicity. [22][23][24] The present study was designed to test the ability of a synthetic cationic polymer, polyethylenimine (PEI), to deliver a SAg, namely the SEA, to tumor cells in vivo and to induce an antitumor immune response and tumor regression. For that purpose, a transmembrane SEA fusion construct (pSEA-TM) was complexed with PEI and injected, in the presence of epinephrine to improve in vivo transfection efficiency, into tumors induced by subcutaneous injection of a melanoma cell line into syngeneic mice.…”