title: Number of treatment cycles influences development of cytotoxic T cells in metastatic breast cancer patients - a phase I/II study.
abstract: The influence of the number of apheresis-stimulation-infusion(s) cycles, and the time in culture before the infusion (one vs. two weeks), on the generation of tumor antigen-specific cytotoxic T-lymphocytes (CTL) was investigated in a phase I/II clinical adoptive immunotherapy trial. Two previously treated metastatic breast cancer patients with no evidence of disease, in complete remission (CR), were enrolled. Each apheretic peripheral blood mononuclear cell (PBMC) sample was stimulated twice with MUC-1 before infusion back into the patients. Killer T-cells responses against MUC-1-expressing MCF-7 (CTL), nonspecific natural killer (NK) and lymphokine-activated killer (LAK) target cell lines, as well as, cytokine production were measured before each infusion. Patients received 2 infusions per month for 4 months. There were no tumor recurrences or toxicity. CTL, NK and LAK cells, type 1 cytokine, gamma-interferon (G-INF), and CD4(+) and CD8(+) memory T-lymphocytes were initially generated, produced or induced, respectively, and then declined. The CTL, NK and LAK cells were only induced at the first infusion of the first month. Thus, maintaining PBMC in culture longer than the first infusion was of no benefit with regards to retaining functional killer T-cells. In conclusion, this study implies that one treatment is optimal.
authors.affiliation: Medical Service, Amarillo Veterans Affairs Health Care System, Amarillo, TX 79106, USA. stephen.wright@med.va.gov
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Wright
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Rewers-Felkins
authors.forename: Imelda S
authors.initials: IS
authors.lastname: Quinlin
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Phillips
authors.forename: Mary
authors.initials: M
authors.lastname: Townsend
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
authors.forename: Paul
authors.initials: P
authors.lastname: Zorsky
authors.forename: Panpit
authors.initials: P
authors.lastname: Klug
authors.forename: Lijun
authors.initials: L
authors.lastname: Dai
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hussain
authors.forename: Aabu A
authors.initials: AA
authors.lastname: Thomas
authors.forename: Chithraleka
authors.initials: C
authors.lastname: Sundaramurthy
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D024221:Antineoplastic Protocols; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016219:Immunotherapy, Adoptive; D007937:Leukapheresis; D018396:Mucin-1 / Q000276:immunology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D018396:Mucin-1