Biologic effects of the adoptive transfer of cells depleted of monocytes with L-phenylalanine methyl ester.
Monocytes macrophages have negative regulatory effects on many immunologic responses. Depletion of monocytes from peripheral blood using the lysosomotropic agent, L-phenylalanine methyl ester (PME), has been shown to improve lymphokine activated killer (LAK) cell expansion in vitro. A pilot study of the adoptive transfer of LAK cells expanded with PME was performed in patients with metastatic renal cell carcinoma. Patients received interleukin-2 (IL-2) by continuous infusion for 5 days. Leukopheresis was performed daily for 4 days during the second week. Cells obtained from 8 patients were depleted of monocytes using PME in an one-step procedure; < or = 3% of the remaining cells were monocytes. All cells were expanded for 10 days in air-porous plastic bags with IL-2. Cells expanded 2.7-fold when depleted with PME and 1.7-fold when not depleted (P = 0.02). Expanded cells were administered together with IL-2. Patients received up to 60 x 10(10) PME-depleted cells (mean = 26 x 10(10)) with LAK activity (% lysis) of 60 +/- 12%. Lymphocyte phenotype and cytolytic activity were not modulated by PME-depletion, and clinical toxicities and systemic immunologic effects observed in patients receiving PME-depleted cells were similar to that of 5 patients receiving cells not expanded with PME. Thus, the use of PME to deplete monocytes ex vivo can result in the yield of large number of effectors that retain immunologic activity for potential clinical use. The process is convenient, efficient, and does not add clinical toxicity.
Triozzi
P L
PL
Department of Internal Medicine, Arthur G. James Cancer Hospital and Research Institute, Ohio State University Comprehensive Cancer Center, Columbus 43210.
Aldrich
W
W
Kim
J
J
Kinney
P
P
Sagone
A
A
Rinehart
J
J
D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007680:Kidney Neoplasms / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000637:transplantation; D009000:Monocytes / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010865:Pilot Projects
C034515:phenylalanine methyl ester; D010649:Phenylalanine