title: Optimal timing for the collection and in vitro expansion of cytotoxic CD56(+) lymphocytes from patients undergoing autologous peripheral blood stem cell transplantation.
abstract: To identify the optimal time for the collection of CD56(+) cytotoxic lymphocytes for adoptive immunotherapy in patients undergoing high-dose chemotherapy (HDCT) and peripheral blood stem cell (PBSC) transplantation, 18 breast cancer patients receiving either three cycles of epirubicin/paclitaxel (CT x 3) followed by HDCT and PBSC transplantation (n = 12) or CTx6 (n = 6) were studied. Blood samples were obtained before each CT/HDCT cycle, from PBSC collections, and repeatedly after autografting for up to 12 months. The number of CD56(+)3(-) and CD56(+)3(+) lymphocytes, their in vitro expandability with interleukin-2, and their cytotoxicity against MCF-7 and Daudi cells were analyzed. Six healthy females served as controls. CD56(+) cell counts in both treatment groups were subnormal but stable during the observation period. The cytotoxicity of the expanded CD56(+) cells was normal and unaffected by the treatment. The in vitro CD56(+) cell expandability (controls, 100 +/- 31-fold, mean +/- SEM) was normal before CT1 and CT2, but reduced in PBSC harvests performed after CT2 and application of G-CSF (21 +/- 6-fold; p < 0.01). After PBSC harvesting, the CD56(+) cell expandability increased to 185 +/- 74-fold and 170 +/- 69-fold (before CT3 and HDCT). This increase was not observed in those patients who did not undergo PBSC mobilization. Two weeks after autografting, the CD56(+) cell expandability was minimal (6 +/- 1-fold), and recovered to 34 +/- 6-fold. Thus, CT, HDCT and autografting do not alter the frequency and inducible cytotoxicity of CD56(+) cells in breast cancer patients. However, the proliferative capacity of CD56(+) cells obtained from PBSC harvests and after autografting is impaired. Therefore, instead of the PBSC graft, maximally expandable CD56(+) cells obtained at least 1 week after PBSC collection should be considered for adoptive immunotherapy after PBSC autografting.
authors.affiliation: Laboratory of Tumor-Biology and Angiogenesis, Division of Hematology & Oncology, University Hospital, 6020 Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Clausen
authors.forename: A L
authors.initials: AL
authors.lastname: Petzer
authors.forename: B
authors.initials: B
authors.lastname: Vergeiner
authors.forename: M
authors.initials: M
authors.lastname: Enk
authors.forename: R
authors.initials: R
authors.lastname: Stauder
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.forename: E
authors.initials: E
authors.lastname: Gunsilius
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D001800:Blood Specimen Collection; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy*; D019002:CD56 Antigen; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D019002:CD56 Antigen; D016179:Granulocyte Colony-Stimulating Factor