USE OF A LETHALLY IRRADIATED MAJOR HISTOCOMPATIBILITY COMPLEX NONRESTRICTED CYTOTOXIC T-CELL LINE FOR EFFECTIVE PURGING OF MARROWS CONTAINING LYSIS-SENSITIVE OR LYSIS-RESISTANT LEUKEMIC TARGETS

Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal resi dual disease. This study investigates the potential of a human major h istocompatibility complex (MHC) nonrestricted killer T-cell line (TALL -104) as a new marrow purging agent in a clinical setting. TALL-104 ce lls can be irradiated without losing cytotoxic activity against tumor targets in vitro. In vivo, the irradiated killers can be adoptively tr ansferred into immunodeficient and immunocompetent leukemia-bearing mi ce, and reverse their disease even in advanced stages. The present stu dy shows that gamma-irradiated TALL-104 cells, cultured for 18 hours w ith marrows from healthy donors, do not impair the viability and long- term growth of committed and pluripotent hematopoietic progenitors. Ho wever, as determined by polymerase chain reaction (PCR) and colony ass ays, TALL-104 cells could completely purge marrows containing up to 50 % lysis-susceptible myelomonocytic leukemia cells (U937). When marrows were admired with a pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in longterm Cr-51-release assays but can be totally growth inhibited by TALL-104 cells in proliferation as says, residual ALL-1 cells were detectable by PCR after TALL-104 purgi ng. However, importantly, these PCR(+) marrows were devoid of tumorige nic activity when transplanted into the human hematopoietic microenvir onment of human severe combined immuno-deficient (SCID) chimeras. Thes e data indicate the strong potential of the TALL-104 cell line in futu re marrow purging strategies against lysis-susceptible and resistant l eukemias. (C) 1996 by The American Society of Hematology.