Anti-CD45 and anti-CD52 (Campath) monoclonal antibodies effectively eliminate systematically disseminated human non-Hodgkin's lymphoma B cells in Scid mice.
Severe combined immunodeficient (Scid) mice inoculated with the human (t(14;18)-positive B cell lines DoHH2 and BEVA develop lethal systemically disseminated lymphoma (de Kroon et al., Leukemia 8:1385, and Blood 80 [suppl 1]:436). These models were used to study the therapeutic effect of rat-anti-human CD52 (Campath-1G) or CD45 monoclonal antibodies (mAbs) on systemically disseminated tumor cells and on tumor cells present in solid tumor masses. Both mAbs were effective in inhibiting growth of systemically disseminated malignant cells. When treatment with anti-CD52 or anti-CD45 mAbs at a dose of 30 micrograms/mouse/d for 4 days was started 24 hours after intravenous inoculation of human DoHH2 or BEVA cells, a 3-log kill of tumor cells was observed as measured by prolonged survival. After treatment, surviving animals injected with high numbers of BEVA cells showed tumor masses in liver, kidney, and mesenteric lymph nodes. In contrast to nontreated animals, however, only low numbers of malignant cells were found in peripheral blood, and bone marrow was free of tumor cells. Similarly, after mAb treatment of mice inoculated subcutaneously (sc) with DoHH2 cells, no tumor cells could be found in the bone marrow, and few DoHH2 cells could be detected in the peripheral blood, spleen, liver, kidney, or lung. In contrast, tumor cells present in subcutaneous tumors and axillary lymph nodes were relatively unaffected by mAb therapy. The presence of rat immunoglobulin (Ig) could be demonstrated on surviving tumor cells. The presence of murine macrophages in areas in these tumors that were depleted of DoHH2 cells suggested that the mAb-mediated antitumor effect observed in the Scid mouse model is mediated by cellular mechanisms. Apparently these mechanisms were not sufficient to eliminate the fast-growing tumor cells present in the protected sites. Our results indicate that treatment with anti-CD52 or anti-CD45 mAbs potentially may be useful as adjuvant immunotherapy for systemically disseminated B cell lymphoma.
de Kroon
J F
JF
Laboratory of Experimental Hematology, Department of Hematology, Leiden University Hospital, The Netherlands.
de Paus
R A
RA
Kluin-Nelemans
H C
HC
Kluin
P M
PM
van Bergen
C A
CA
Munro
A J
AJ
Hale
G
G
Willemze
R
R
Falkenburg
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000276:immunology*; D000074301:CD52 Antigen; D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D004273:DNA, Neoplasm / Q000032:analysis; D006023:Glycoproteins; D006801:Humans; D007074:Immunoglobulin G; D016130:Immunophenotyping; D007167:Immunotherapy; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008297:Male; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C000613864:Cd52 protein, rat; D004273:DNA, Neoplasm; D006023:Glycoproteins; D007074:Immunoglobulin G; D017493:Leukocyte Common Antigens