Antitumor effect of thymosin alpha 1/interleukin-2 or thymosin alpha 1/interferon alpha,beta following cyclophosphamide in mice injected with highly metastatic Friend erythroleukemia cells.
We investigated the effects of the systemic administration of thymosin alpha 1 plus relatively low doses of human recombinant interleukin-2 or very low doses of interferon alpha,beta in untreated and cyclophosphamide (CY)-treated DBA/2 mice challenged either subcutaneously or intravenously (i.v.) with Friend erythroleukemia cells (FLC). Both treatments resulted in the complete regression of subcutaneous tumor and cured a significative percentage of mice. They also increased the survival time of mice i.v. injected with large numbers of FLC. Neither immunotherapy alone nor CY, alone or in combination with single cytokines, produced similar effects. The antitumor action of these combined chemoimmunotherapy protocols seems to involve activation of the immune response since (a) a synergistic increase of the cytotoxicity of spleen cells was demonstrated in treated mice; (b) selective in vivo depletion of asialo-GM1, CD4, or CD8-positive cells abrogated this antitumor activity; and (c) a high lymphoid cell infiltration was found at the tumor site and in the livers of treated mice.
Garaci
E
E
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Pica
F
F
Mastino
A
A
Palamara
A T
AT
Belardelli
F
F
Favalli
C
C
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D005622:Friend murine leukemia virus; D005677:G(M1) Ganglioside / Q000276:immunology; D016898:Interferon-alpha / Q000008:administration & dosage; D016899:Interferon-beta / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D004915:Leukemia, Erythroblastic, Acute / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D007942:Leukemia, Experimental / Q000517:prevention & control; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives; D014412:Tumor Virus Infections / Q000517:prevention & control*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016898:Interferon-alpha; D007376:Interleukin-2; D005677:G(M1) Ganglioside; D013947:Thymosin; C018835:asialo GM1 ganglioside; D016899:Interferon-beta; D003520:Cyclophosphamide; D000077596:Thymalfasin