Antitumor and accessory immune activities of peripheral blood stem cells mobilized with granulocyte-macrophage colony-stimulating factor.
The characteristics of PBSC mobilized with GM-CSF, which has been shown to augment monocyte/macrophage (Mo/Mx) antitumor and accessory activities, were evaluated. Patients with metastatic cancers were treated with GM-CSF at 5 micrograms/kg sc, days 1 to 7; leukaphereses were performed on days 6 and 7. A mean of 3.3 x 10(10) mononuclear cells were collected, 59% of which were lymphoid and 32%, monocytoid. Spontaneous Mo/Mx tumor cell cytotoxicity was not detectable in the leukapheresis product, either before or after cryopreservation; Mo/Mx tumor cell cytotoxicity, however, was inducible in vitro with IFN-gamma. Likewise, spontaneous lymphocyte cytotoxicity was not detectable in the leukapheresis product; lymphokine-activated killer cell activity was inducible in vitro with IL-2. Whereas lymphoproliferative responses to tetanus toxoid of cryopreserved PBSC were less than that of freshly collected PBSC, the capacity of Mo/Mx from cryopreserved PBSC to function as accessory cells in the lymphoproliferative response was maintained. These results indicate that significant numbers of immune cells can be mobilized with GM-CSF alone. Cryopreserved, GM-CSF-mobilized PBSC do not demonstrate spontaneous antitumor cytolytic activity; however, accessory activity is present and antitumor cytolytic activity mediated by both monocytoid and lymphoid cells is inducible.
Triozzi
P L
PL
Ohio State University Comprehensive Cancer Center, Arthur G James Cancer Hospital and Research Institute, Columbus, USA.
Tucker
F
F
Benzies
T
T
Balcerzak
S P
SP
D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001793:Blood Preservation; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D001855:Bone Marrow Diseases / Q000139:chemically induced; D003131:Combined Modality Therapy; D015925:Cryopreservation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007937:Leukapheresis; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D007376:Interleukin-2; D011994:Recombinant Proteins; D013745:Tetanus Toxoid; C081222:sargramostim; D003606:Dacarbazine; D004317:Doxorubicin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007069:Ifosfamide