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The effects of postoperative immunization with purified tumor-associated antigens on the development of lung metastases following excision of the Lewis lung carcinoma (3LL) were investigated. Soluble tumor-associated antigens were isolated from 3LL cells by detergent solubilization and purified by affinity chromatography on peanut agglutinin (PNA)-agarose. The immunization with subcutaneous injections of PNA-binding glycoproteins (PNA receptors) at the early phase following excision of primary footpad tumors of 3LL resulted in a significant decrease in incidence and size of lung metastases. The delayed immunization, however, failed to suppress the development and growth of metastatic lung tumors after surgery. The suppression in postoperative development of lung metastases was found to depend on the scheduling of immunization following local tumor excision. Splenectomy performed simultaneously with amputation of the tumor-bearing leg completely abolished the decrease in the development and growth of postoperative lung metastases in immunized mice. The involvement of the lymphoid system in the control of metastatic tumor growth was also confirmed in an in vivo tumor neutralization assay utilizing the spleen cells.
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