ACTIVE SPECIFIC IMMUNOTHERAPY OF A MURINE MAMMARY ADENOCARCINOMA USING A SYNTHETIC TUMOR-ASSOCIATED GLYCOCONJUGATE

  • 15 July 1990
    • journal article
    • research article
    • Vol. 50  (14) , 4308-4314
Abstract
A synthetic tumor-associated glycoconjugate (S-TAG) "vaccine" formulation was develped for active specific immunotherapy of a murine mammary adenocarcinoma (TA3-Ha). An S-TAG composed of the Thomsen Freidenreich hapten coupled to a conventional carrier protein (key-hole limpet hemocyanin) and emulsified in Ribi adjuvant, when administered s.c. (in four doses at 3 to 6 days apart) into hosts bearing TA3-Ha tumors, provided 25% long-term survival. When administration of this synthetic glycoconjugate was preceded by treatment with cyclophosphamide (100 mg/kg i.v.), 50% long-term survival was observed for hosts in which the tumor had been established for 5 days and up to 90% longterm survival for groups of mice with tumors established for 1 to 2 days. In contrast, a significantly (P < 0.025) lower level of survival was observed when cyclophosphamide treatment was preceded by active immunizations with the S-TAG tumor vaccine. Surviving tumor-challenged mice that had been treated with cyclophosphamide and the S-TAG vaccine had relatively good IgG antibody and delayed-type hypersensitivity responsiveness to the synthetic Thomsen Friedenreich determinants. About 30% of these animals were also able to resist and sustain long-term survival when rechallenged with a high dose (1 .times. 104) of TA3-Ha tumor cells. Lymph node cells obtained from surviving animals were highly inhibitory to tumor growth in a Winn-type assay.