Human breast carcinoma patients develop clonable oncofetal antigen-specific effector and regulatory T lymphocytes

Oncofetal Ag (OFA) isa 44-kDa glycoprotein expressed during early to mid-ge station fetal development and re-expressed as a surface Ag by tumor cells s oon after transformation. The Ag is detectable on all types of human and ro dent tumors tested,but is undetectable on normal cells, In experimental ani mals it is autoimmunogenic and induces Potentially protective T cell respon ses both after experimental immunization and during tumor development subse quent to carcinogenic insult. To determine whether this tumor-associated Ag is also immunogenic for human T lymphocytes, breast carcinoma patients' pe ripheral blood mononuclear leucocytes were stimulated in vitro with autolog ous tumor cells in the presence of IL-2, gamma-IFN, and IL-6 for 2 wk, The tumor-reactive cells were then restimulated and cloned by limiting dilution , and the clones were analyzed. We established 24, 19, 11, and 16 tumor-rea ctive clones from the four respective patients. Of those, 4, 6, 4, and 7, r espectively, proliferated specifically to purified OFA, Both CD4 and CD8 OF A-specific clones were established, which responded equally well to purifie d OFA or 32- to 44-kDa immature laminin receptor protein. All were CD3(+), TCR-alpha beta(+). All CD4 clones secreted gamma-IFN, but neither secreted IL-4 nor IL-10. Both IFN-gamma-secreting cytotoxic CD8 clones and IL-10-sec reting inhibitory CD8 clones were established. Thus, during human cancer de velopment, the same types of OFA-specific effector and regulatory T Cells a re induced as during murine T lymphomagenesis.