Immunotherapy against murine leukemia.
The central hypothesis underlying specific anti-leukemia immunotherapy is that leukemic cells express antigenic determinants not expressed on their counterpart normal adult cells. We have developed a murine myeloid leukemia/tumor immunization model using the low-immunogenic WEHI3 leukemia in syngeneic mice. Mice preimmunized with irradiated, transduced IL-7-producing WEHI3 cells showed systemic protection and rejection of a lethal dose of intravenously (i.v.) injected parental WEHI3 cells (5 x 10(4)) with 40% long-term survival. When vaccinated with a mixture of parental WEHI3 cells and IL-2-producing NIH-3T3 fibroblasts (5 x 10(5)), 60% survival was observed. Vaccination with murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing WEHI3 cells resulted in only 20% survival of i.v. challenged mice, and the additional combination of IL-2- and IL-7-producing vaccine did not reveal any additive or synergistic effects. Immunizing mice with a pre-established leukemia burden (injected with 5 x 10(4) WEHI3 cells, i.v., 3 days prior to immunization) did not cure or result in a prolongation of survival, indicating that improved methods of immunization are needed. Taken together, we have identified IL-7 and IL-2 as effective cytokines in our leukemia/vaccination model with only marginal activity by GM-CSF.
de Vos
S
S
Division of Hematology/Oncology, Cedars-Sinai-Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Kohn
D B
DB
Cho
S K
SK
McBride
W H
WH
Said
J W
JW
Koeffler
H P
HP
D016475:3T3 Cells; D000818:Animals; D019496:Cancer Vaccines; D002460:Cell Line; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000096:biosynthesis; D007942:Leukemia, Experimental / Q000628:therapy*; D015479:Leukemia, Myelomonocytic, Acute / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid
D019496:Cancer Vaccines; D007376:Interleukin-2; D015851:Interleukin-7; D011994:Recombinant Proteins