Successful immunotherapy of the highly metastatic murine ESb lymphoma with sensitized CD8+ T cells and IFN-alpha/beta.
Daily IFN-alpha/beta therapy was totally ineffective in inhibiting the development of visceral metastases in DBA/2 mice injected i.v. with the ESb lymphoma regardless of the number of tumor cells injected. The finding that IFN-alpha/beta therapy increased the survival time of ESb-immunized mice rechallenged with ESb cells suggested that cooperation between the immune system and IFN-alpha/beta was important. Adoptive transfer of Esb-immune spleen cells (but not normal cells) together with IFN-alpha/beta treatment did inhibit the development of ESb metastases in immunocompetent DBA/2 mice. Either treatment alone was ineffective. The anti-metastatic effect was specific for the ESb lymphoma as spleen cells from ESb-immunized mice together with IFN-alpha/beta treatment did not inhibit the development of metastases in mice challenged with IFN-alpha/beta-resistant 3C18 FLC. Depletion of CD8+ T cells (but not CD4+ T cells or B lymphocytes) prior to transfer eliminated the protective effect of ESb-immune splenocytes in IFN-alpha/beta-treated mice. As few as 1 x 10(6) ESb-immune spleen cells highly enriched for CD8+ cells increased the survival time of IFN-alpha/beta-treated ESb-challenged DBA/2 mice. The combined therapy of ESb-specific immune cells and IFN-alpha/beta resulted in long-term immunity to this tumor.
Kaido
T
T
Laboratory of Viral Oncology, Groupe de Laboratoires de l'Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Maury
C
C
Schirrmacher
V
V
Gresser
I
I
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016827:CD8 Antigens / Q000276:immunology*; D003131:Combined Modality Therapy; D005260:Female; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000627:therapeutic use*; D008223:Lymphoma / Q000188:drug therapy / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D016827:CD8 Antigens; D007370:Interferon Type I