Successful immunotherapy of the highly metastatic murine ESb lymphoma with sensitized CD8 + T cells and IFN‐α/β

Daily IFN‐α/β 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‐α/β therapy increased the survival time of ESb‐tmmunized mice rechallenged with ESb cells suggested that cooperation between the immune system and IFN‐α/β was important. Adoptive transfer of ESb‐immune spleen cells (but not normal cells) together with IFN‐α/β 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‐α/β treatment did not inhibit the development of metastases in mice challenged with IFN‐α/β‐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‐α/β‐treated mice. As few as 1 × 10 6 ESb‐immune spleen cells highly enriched for CD8 + cells increased the survival time of IFN‐α/β‐treated ESb‐challenged DBA/2 mice. The combined therapy of ESb‐specific immune cells and IFN‐α/β resulted in long‐term immunity to this tumor. © 1994 Wiley‐Liss, Inc.