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Induction of -N-Acetylgalactosamine-O-Serine/Threonine (Tn) Antigen-mediated Cellular Immune Response for Active Immunotherapy in Mice¹

The Biomembrane Institute, Seattle, Washington 98119, and University of Washington, Seattle, Washington 98195

A block in carbohydrate chain elongation of O-glycosylated mucins results in accumulation of -GalNAc O linked to serine or threonine (Tn antigen) in a large percentage of human adenocarcinomas. Immunization of mice with desialylated ovine submaxillary mucin (A-OSM), which contains a large concentration of Tn antigen, provided protection against challenge of a highly invasive Tn expressing syngeneic mouse mammary tumor, TA3-Ha. A similar protective effect was not observed in mice immunized with the deglycosylated mucin or irridiated TA3-Ha cells. Immunization with A-OSM but not with deglycosylated mucin resulted in high anti-Tn antibody response in mice. A-OSM induced in vitro proliferation of T-lymphocytes obtained from mice preimmunized with A-OSM or irradiated TA3-Ha cells. This antigen-specific T-cell response was significantly lower if lymphocytes were stimulated with either the deglycosylated or sialylated form of mucin. A-OSM stimulation induced primarily a CD4⁺ T-cell population, and these cells secreted interleukin 2 in a dose-dependent fashion. A-OSM was also able to induce delayedtype hypersensitivity in mice in response to footpad injections with irradiated TA3-Ha cells. These studies indicate that Tn antigen presented on a protein backbone is capable of providing cellular immunity and protection against tumor in mice.

¹ These studies were supported by NIH Outstanding Investigator Grant CA42505 and funds from The Biomembrane Institute.

² To whom requests for reprints should be addressed at The Biomembrane Institute, 201 Elliott Avenue West, Seattle, WA 98119.

Received 10/15/90. Accepted 12/20/90.

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