Use of a lethally irradiated major histocompatibility complex nonrestricted cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive or -resistant leukemic targets.
Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal residual disease. This study investigates the potential of a human major histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a new marrow purging agent in a clinical setting. TALL-104 cells can be irradiated without losing cytotoxic activity against tumor targets in vitro. In vivo, the irradiated killers can be adoptively transferred into immunodeficient and immunocompetent leukemia-bearing mice, and reverse their disease even in advanced stages. The present study shows that gamma-irradiated TALL-104 cells, cultured for 18 hours with marrows from healthy donors, do not impair the viability and long-term growth of committed and pluripotent hematopoietic progenitors. However, as determined by polymerase chain reaction (PCR) and colony assays, TALL-104 cells could completely purge marrows containing up to 50% lysis-susceptible myelomonocytic leukemia cells (U937). When marrows were admixed with a pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in longterm 51Cr-release assays but can be totally growth inhibited by TALL-104 cells in proliferation assays, residual ALL-1 cells were detectable by PCR after TALL-104 purging. However, importantly, these PCR+ marrows were devoid of tumorigenic activity when transplanted into the human hematopoietic microenvironment of human severe combined immunodeficient (SCID) chimeras. These data indicate the strong potential of the TALL-104 cell line in future marrow purging strategies against lysis-susceptible and -resistant leukemias.
Wistar Institute, Philadelphia, PA 19104, USA.
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A
Cesano
G
G
Pierson
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S
Visonneau
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AR
Migliaccio
D
D
Santoli
D000818:Animals; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation; D016025:Bone Transplantation; D002051:Burkitt Lymphoma / Q000473:pathology; D002648:Child; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000166:cytology; D016332:Fetal Tissue Transplantation; D005720:Gamma Rays; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D007938:Leukemia / Q000473:pathology* / Q000628:therapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D018365:Neoplasm, Residual; D009369:Neoplasms / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects / Q000637:transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins