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Although replication-competent viruses have been developed to treat cancers, their cytotoxic effects are insufficient, as infection is inhibited by the generation of neutralizing antibodies. To address this limitation, we developed a carrier cell system to deliver a replication-competent adenovirus. Carrier cells infected with replication-competent adenovirus were incubated with target cancer cells in a high titer of anti-adenovirus antibody. Carrier cells were injected into syngeneic subcutaneous tumors after immunization with adenovirus. Carrier cell-derived cell fragments containing viral particles were engulfed by proliferative target cancer cells. This engulfment-mediated transfer of adenovirus was not inhibited by the anti-adenovirus antibody and enabled repetitive infection. After the induction of anti-adenoviral cytotoxic T-lymphocyte (CTL) responses by immunization with adenovirus, administration of carrier cells infected with a replication-competent adenovirus induced complete tumor regression. Adenovirus-GM-CSF augmented the anti-tumor effect of carrier cells by increasing anti-adenoviral and anti-tumoral CTL responses and decreased the number of injections of carrier cells required to induce complete tumor regression. This novel carrier cell-mediated viral transfection system might prove useful in a variety of cancer therapies.

Background. Alterations of the p53 gene are involved in the development of diverse human malignancies, but their incidence and clinicopathologic features are still not well characterized for endometrial carcinoma. Methods. To investigate the clinicopathologic significance of p53, mutations and loss of heterozygosity (LOH) in endometrial carcinoma in 92 patients with this disease were examined. Results. Mutations of p53 were detected in 20 (22%) of the 92 patients with carcinoma, and LOH was detected in 23 (32%) of the 72 patients in whom heterozygosity of the gene was available. There was a significant correlation between the occurrence of mutation and LOH. Mutations and LOH were more frequent in patients with Grade 3 tumors than in those with Grades 1 and 2 tumors (P = 0.0498, P = 0.0051, respectively). Patients with LOH had a poorer postoperative survival than those without LOH (P = 0.0022, log‐rank test), and patients with both LOH and mutation showed the worst prognosis (P < 0.0001, log rank test). Loss of heterozygosity of the p53 gene showed a significant relation to prognosis that was independent of tumor stage, histologic grade, and muscular invasion. Conclusions. Mutation and LOH of the p53 gene are prognostic indicators in patients with endometrial carcinoma, suggesting that alterations of p53 may play an important role in the development of this cancer.

Adenoviral vectors are commonly used in gene therapyimmunized animals treated with etoposide or cyclophostrials because of their efficiency in gene transfer. However, phamide. Neutralizing antibodies to adenovirus and cytotheir use is limited by cellular and humoral immune toxic T lymphocyte (CTL) lysis of virally transduced cells responses that result in temporary transgene expression were significantly suppressed in mice treated with etopoand reduced efficacy of repeated vector administration. We side at 2 or 10 mg/kg/day or cyclophosphamide at 10 hypothesized that certain oncolytic agents commonly used mg/kg/day compared with untreated mice (P Ͻ 0.05). Sigto treat cancer patients could suppress the immune nificantly larger areas of gene transduction were observed response to adenoviral vectors, and enable repeated adenin treated animals compared with untreated mice or the ovirus-mediated cancer gene therapy. Etoposide and mice treated with cyclophosphamide at 2 mg/kg/day (P Ͻ cyclophosphamide were tested for their ability to suppress 0.05). Our results suggest that repeated adenovirally the humoral and cellular immune responses to an adenomediated gene therapy is achievable in cancer patients viral vector in immunocompetent C3H mice. Intratumoral who are concurrently undergoing treatment with chemotransgene expression was monitored in adenovirustherapy.

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