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Generation of Monoclonal Antibodies against Human Lung Squamous Cell Carcinoma and Adenocarcinoma Using Mice Rendered Tolerant to Normal Human Lung

Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo, Japan 194

Four murine monoclonal antibodies against human lung carcinoma were generated using a novel immunization procedure. BALB/c mice were rendered neonatally tolerant to normal human lung tissues and subsequently immunized with human lung tumor tissues. The lower level of antibody-reactivity to the tolerogen was seen in the sera of mice rendered neonatally tolerant as compared with the level of reactivity in the sera of nontolerant mice. The mice which maintained a sufficiently tolerant state were selected for hybridoma production. Two monoclonal antibodies, KM-32 and KM-34, were developed from mice immunized with lung squamous cell carcinoma tissues and two other monoclonal antibodies, KM-52 and KM-93, were developed from mice immunized with lung adenocarcinoma tissues. Distribution of antigens detected by the monoclonal antibodies was investigated by enzyme-linked immunosorbent assay using membrane fractions prepared from a number of tumorous and normal tissues and various human normal and tumor cell lines. KM-32 recognized a carbohydrate antigen expressed predominantly on lung squamous cell carcinoma cells and its carbohydrate structure appeared to be associated with blood group A antigen. KM-93 recognized a sialylated carbohydrate epitope on the antigen expressed on lung adenocarcinoma cells and a few other tumor cells. KM-34 and KM-52 detected protein or glycoprotein antigens and they showed predominant reactivity to lung squamous cell carcinoma and lung adenocarcinoma, respectively. KM-32 and KM-34 antibodies showed complement-dependent cytotoxicity against a lung tumor cell line.

These results suggest that the tolerance technique is useful for efficient screening of murine monoclonal antibodies specific to human tumors. The efficacy of these four monoclonal antibodies in diagnosis and therapy of lung cancer will be the subject of a sequential study.

¹ To whom requests for reprints should be addressed.

Received 11/26/85. Revised 4/29/85. Accepted 5/21/86.

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