Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate.
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 less than 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 10(4] of TA3-Ha tumor cells. Lymph node cells obtained from surviving animals were highly inhibitory to tumor growth in a Winn-type assay.
Fung
P Y
PY
Department of Immunology, University of Alberta, Edmonton, Canada.
Madej
M
M
Koganty
R R
RR
Longenecker
B M
BM
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate; D002460:Cell Line; D003520:Cyclophosphamide / Q000627:therapeutic use; D004187:Disaccharides / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D006001:Glycoconjugates / Q000627:therapeutic use*; D007167:Immunotherapy; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D004337:Drug Carriers; D006001:Glycoconjugates; D014614:Vaccines, Synthetic; C016467:Thomsen-Friedenreich antigen; C025991:Thomsen-Friedenreich antibodies; D003520:Cyclophosphamide