Loss of oncogenicity and concomitant increased immunogenicity of murine plasmacytoma cell lines.

Murine plasmacytoma cells gradually decrease in oncogenicity with prolonged culture in vitro. Newly established cultures are oncogenic and cause lethal tumors. Subsequently, the cultures are oncogenic but some of the tumors regress. Later in the life of the culture none of the tumors are lethal. The longer the cells are in culture, the less oncogenic they become; eventually the cultures are nononcogenic in normal mice but do cause tumors in irradiated mice. Clones from the cultures vary from being very oncogenic to being nononcogenic. It appears that the nononcogenic cells have a selective growth advantage and become the dominant cell type in the cultures. Nononcogenic cultures are more effective for immunization to subsequent challenge with the original tumor than are the tumor cells or oncogenic cultures and may confer complete protection against lethal tumor challenge in adoptive transfer experiments. Mixtures of nononcogenic and oncogenic cells decrease the tumor-forming ability of the latter when they are injected together in one site or injected separately in two sites.