A new approach to adoptive immunotherapy of cancer using tumorcytotoxic macrophages grown from peripheral blood monocytes.
Clinical trials to evaluate the potential of adoptive immunotherapy in cancer patients have been restricted to the use of lymphoid effector cells. Of the other probably even more important host defense system against tumor growth, the mono-nuclear phagocyte system, only monocytes (mo) have been reinfused which, however, represent immature precursor cells and acquire full functional competence only upon further maturation. This is a report on 7 patients who received autologous macrophages (MO) grown in vitro from blood mo and activated by interferon-gamma (IFN gamma). Mononuclear cells were isolated from whole blood by cytapheresis and cultured for 7 days with 2% autologous serum on hydrophobic Teflon foils. Eighteen house before cell harvest, recombinant human IFN gamma was added at 200 IU/ml. Mo-derived MO were purified by counter-current elutriation. Starting with 10(8) MO cells, therapy was escalated up to the maximal number of MO obtainable from one single preparation cycle. Currently, 26 therapies have been performed with the maximal dose being 1.7 x 10(9) MO per infusion. Except for low grade fever (less than 38 degrees C), MO autografts were well tolerated, with no side effects observed. Biological response was followed by analyzing the serum levels of beta 2-microglobulin, neopterin, interleukin-6, tumor necrosis factor, and lysozyme. While in 3 out of 7 patients serum neopterin increased in response to MO therapy, other biological response parameters remained at pretreatment levels. Radiolabeled MO were shown to first accumulate in the lungs, then to pool into liver and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
Andreesen
R
R
Medizinische Klinik der Albert-Ludwigs-Universität, Freiburg, Germany.
Scheibenbogen
C
C
Brugger
W
W
Krause
S
S
Leser
H G
HG
Kopf
S
S
Engler
H
H
Schümichen
C
C
Löhr
G W
GW
D001708:Biopterins / Q000031:analogs & derivatives / Q000032:analysis; D002465:Cell Movement; D002478:Cells, Cultured; D016238:Cytapheresis; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009000:Monocytes; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019798:Neopterin; D010865:Pilot Projects; D011994:Recombinant Proteins; D014182:Transplantation, Autologous
D011994:Recombinant Proteins; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma; D005337:Fibrin; D005340:Fibrinogen