Kaori Okugawa

Immunotherapy of solid cancer using dendritic cells pulsed with the HLA-A24-restricted peptide of carcinoembryonic antigen.

Abstract. Carcinoembryonic antigen (CEA), an oncofetal glycoprotein overexpressed in most gastrointestinal and lung cancers, is a candidate molecule for cancer immunotherapy. Recently, a CEA-derived 9-mer peptide, CEA652 (TYACFVSNL), has been identified as the epitope of cytotoxic T lymphocytes restricted with human leukocyte antigen (HLA)-A24, which is present in 60% of the Japanese population and in some Caucasians. The authors performed a clinical study of a vaccine using autologous dendritic cells (DCs) pulsed with CEA652 and adjuvant cytokines, natural human interferon alpha (nhuIFN-α), and natural human tumor necrosis factor alpha (nhuTNF-α), for the treatment of patients with CEA-expressing advanced metastatic malignancies. Ten HLA-A24 patients with advanced digestive tract or lung cancer were enrolled in the study to assess toxicity, tolerability and immune responses to the vaccine. DCs were generated from plastic adherent monocytes of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMCs) in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). Generated DCs showing an immature phenotype were loaded with CEA652 and injected into patients intradermally and subcutaneously with 50% of the dose administered by each route every 2 weeks for a total of ten vaccinations. The total dose of administered DCs ranged from 2.7×107 cells to 1.6×108 cells. Adjuvant cytokines, i.e., 1×106 U/body of nhuIFN-α and nhuTNF-α, were administered to patients twice a week during the vaccination period. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. In the delayed-type hypersensitivity (DTH) skin test, two patients showed a positive skin response to peptide-pulsed DCs after vaccination, although none of the patients tested positive prior to vaccination. In the two patients who showed a positive skin response disease remained stable for 6 and 9 months respectively. These results suggest that active immunization using DCs pulsed with CEA652 peptide in combination with the administration of adjuvant cytokines is a safe and feasible treatment procedure.

Primary hepatic Burkitt's Lymphoma with chronic hepatitis C

The liver is an uncommon primary site for malignant lymphoma, and primary hepatic lymphoma has been found to make up 0.4% of all extranodal lymphomas. We report a rare case of a 75-year-old Japanese male with primary hepatic Burkitt’s lymphoma, according to both the revised European-American Lymphoma classification and the new World Health Organization classification. As not only histological findings but also immunological features are deemed essential in the diagnosis of Burkitt’s lymphoma, the previous 7 cases of primary hepatic Burkitt’s lymphoma were not fully evaluated, using these criteria. As far as we know, this is the first case of primary hepatic Burkitt’s lymphoma with typical features on histological, immunological and cytogenetical analysis. He had a history of chronic hepatitis C over several decades with subsequent liver cirrhosis. From our review of the literature and our case, the relationship between hepatitis C virus infection and the development of primary hepatic Burkitt’s lymphoma remains obscure.

A CASE OF GRAVES' DISEASE WITH AN ENORMOUS GOITER

症例は33歳,男性.主訴は頸部腫脹.バセドウ病のため他院で抗甲状腺剤,β遮断剤の内服治療を受けていたが, 1年前より急激に甲状腺腫が増大し内科的治療が困難になってきたため,自ら手術を希望し当院に紹介受診となった.受診時は首回りが50cmにもおよぶ巨大甲状腺腫でかつ機能亢進状態にあった.手術時大量出血が予想されたため自己血1,200mlを準備し,ヨウ化カリウム,ステロイド,炭酸リチウムで甲状腺機能抑制を図ったが充分なホルモン分泌抑制が得られないまま甲状腺亜全摘術を施行した.摘出甲状腺重量は786g,術中出血量1,715ml,手術時間9時間54分,推定残置量は3.2gだった.術後一過性甲状腺機能過剰状態と左反回神経麻痺を呈した.術後7カ月目現在首回りは38cm,甲状腺機能低下症を呈しているためレボチロキシンナトリウム(チラーヂンS®)を内服中である.巨大な甲状腺腫に対して外科的治療は非常に有効であるが,推定甲状腺重量が200gを超えると手術手技的難易度が格段に上昇するため,内科的,放射線的治療に抵抗性を有すると判断された場合は,甲状腺腫が大きくなる前に速やかに外科的治療に切り替えるべきであると考えられた.