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Active Specific Immunotherapy of a Murine Mammary Adenocarcinoma Using a Synthetic Tumor-associated Glycoconjugate¹

Department of Immunology, University of Alberta, Edmonton, Alberta T6G 2H7 [P. Y. S. F., B. M. L.], and Biomira, Inc., Research Centre One, Edmonton Research and Development Park, Edmonton, Alberta T6N 1E5 [R. R. K., B. M. L.], Canada

A synthetic tumor-associated glycoconjugate (S-TAG) "vaccine" formulation was developed 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 (keyhole 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% long-term 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 x 10⁴) of TA3-Ha tumor cells. Lymph node cells obtained from surviving animals were highly inhibitory to tumor growth in a Winn-type assay.

¹ This work was supported by a grant from National Cancer Institute of Canada and by Biomira, Inc.

² Deceased and to whom this paper is dedicated.

³ To whom requests for reprints should be addressed.

Received 10/18/89. Revised 2/ 1/90.

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