Adoptive immunotherapy of a syngeneic murine leukemia with a tumor-specific cytotoxic T cell clone and recombinant human interleukin 2: correlation with clonal IL 2 receptor expression.
The successful adoptive immunotherapy of the syngeneic Friend virus-induced murine leukemia FBL-3 was mediated by a proliferative MHC-restricted, tumor-specific CTL clone in combination with recombinant human IL 2. This clone was previously shown to express the L3T4-, Lyt-1+, Lyt-2+ surface phenotype. Activation of the clone for 48 hr in vitro with irradiated tumor cells induced the expression of IL 2 receptors and markedly increased clonal proliferation in response to recombinant IL 2. Intravenous injection of 2 X 10(7) 48 hr in vitro-activated cloned cells, followed by 6 days of systemic (i.p.) administration of IL 2 resulted in the complete regression of tumors and the cure of 50% of the treated mice. IL 2 alone had no effect on tumor growth, whereas the injection of nonactivated (resting) clone plus IL 2 or activated clone without IL 2 had small but insignificant effects on tumor growth and survival. These results indicated that the in vivo effector functions of cloned T cells may be markedly enhanced by the concurrent systemic administration of recombinant IL 2 and by the induction of optimal IL 2 receptor expression on the cloned T cells at the time of cell administration.
L A
LA
Matis
S
S
Shu
E S
ES
Groves
S
S
Zinn
T
T
Chou
A M
AM
Kruisbeek
M
M
Rosenstein
S A
SA
Rosenberg
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*
D000957:Antigens, Viral, Tumor; D000939:Epitopes; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins