Progress reports on immune gene therapy for stage IV renal cell cancer using lethally irradiated granulocyte-macrophage colony-stimulating factor-transduced autologous renal cancer cells.

There is no effective treatment for patients with stage IV renal cell cancer (RCC), although the introduction of new therapy is imminent. Cancer gene therapy is currently considered to be one of the most promising therapeutic modalities in the field of cancer treatment. Based on the results of animal studies, vaccination using autologous granulocyte-macrophage colony-stimulating factor-transduced renal cancer cells appears promising. Before initiating a clinical study using an ex vivo gene-transduced autologous cell vaccine-based immunogene therapy for RCC in Japan, in 1992 we initially planned a Japanese version of a clinical protocol in collaboration with a US group. In 1993, the original protocol was refined. We performed five preclinical qualification studies using RCC nephrectomy specimens from patients in 1997, and the results showed that preparation of RCC cells for autologous vaccines at the Clinical Cell Technology Facility, Research Hospital of the Institute of Medical Science, University of Tokyo, was feasible. Subsequently in August 1998, the Ministry of Health and Welfare and the Ministry of Education, Science, Culture, and Sport approved our clinical protocol. We have recruited two patients with stage IV RCC to our study so far. Here we report the background to the initiation of cancer gene therapy in Japan.

[Immunohistochemical study on the expression of perforin in tumor infiltrating lymphocytes of renal cell carcinoma].

Perforin is considered to be one of the important cytolytic factors found in the granules of killer cells. In this paper we attempted to demonstrate perforin in TIL (tumor infiltrating lymphocytes) of 55 human renal cell cancer cases and the perforin was proved by staining immunohistochemically with an anti-PFP monoclonal antibody. The result indicated that perforin was observed in 98% of the cases, while few positive cell was found in normal renal tissues. TILs were further characterized into their subsets including CD4+ T cells, CD8+ T cells, NK cells and gamma/delta T cells using antibodies specific to their surface markers. The antibodies used are anti-Lew3a, anti-Lew2a, anti-Lew19 and anti-delta chain antibody. The former two subsets were predominantly found to be infiltrating in the tumor tissue, while the latter two subsets were shown to be lesser than the former. For examination of the correlation between the presence of perforin and the characteristics of infiltrated lymphocyte subsets, double-staining of the cells was performed using anti-perforin and one of anti-surface marker antibodies, respectively. The perforin was found to be expressed on the four subsets at different extent. A stronger reactivity of the perforin was found in the CD4+ T cells and CD8+ T cells than that in the NK cells and the gamma/delta T cells. These findings suggest that perforin may play a role of effector functions in the immunological defense mechanism against cancer. To define the significance of the expression of the perforin not only on the CD8+ T cells but also on the CD4+ T cells is required for further study.

[Metastasis of hepatocellular carcinoma to the urinary bladder]. / Metastase eines hepatozellulären Karzinoms in die Harnblase.

We report a case of metastasis of a hepatocellular carcinoma to the bladder. Clinically the tumor was suspected to be a primary bladder tumor with subsequent metastasis to the liver. However, the pathological diagnosis yielded different results. The tumor cells resembled liver cells and sometimes bile production was even observed. No therapy was available and the patient died of cachexia 6 months later.

Papillary renal cell carcinoma. Report of two cases.

Papillary renal cell carcinoma is an uncommon variant of renal cell carcinoma which has unique features including hypovascularity or avascularity, extensive stromal macrophage infiltration and better prognosis than that for nonpapillary renal cell carcinoma. Two cases of papillary renal cell carcinoma presenting hypovascular or avascular angiology are presented. Histologically, the two tumors had a purely papillary structure. Papillae were lined by a layer of epithelial cells which lacked prominent cellular atypia, and there were numerous macrophages in the stroma. In addition, in one patient, extensive calcification of the tumor capsule was present. Furthermore, our experience in the present study with imprint cytology indicates that it offers corroborative information for the intraoperative diagnosis made on the basis of frozen section examination.