Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy

Abstract

One new approach to cancer therapy is based on the adoptive transfer of tumor-specific cytotoxic T cells and anti-CD25 antibodies. In the present study, CD8 + and IFN-γ secreting T lymphocytes (CTLs) were enriched as tumorspecific cytotoxic T cells from spleen lymphocytes of mice bearing the Renca tumor (a murine renal carcinoma line originating from a BALB/c mouse) after stimulation with tumor cells. An anti-CD25 IL-2Rα(anti-CD25) mAb from hybridoma PC61 was used for depletion for CD4 + CD25 + regulatory T (Treg) cells. Treatment-efficacy for tumor-bearing mice was compared using 4 systems: 1, whole spleen lymphocytes stimulated with tumor cells in vitro from tumor-bearing mice; 2, CTLs; 3, anti-CD25 mAbs; 4, CTLs and anti-CD25 mAbs. At the 50th day after tumor inoculation, in the group which received anti-CD25 mAb for depletion of T cells and inoculation of CTLs, tumors had disappeared and no regrowth was observed. In contrast, all mice of the non-treated and other three groups, treated with whole spleen cells alone, CTLs alone and anti-CD25 mAb alone, had died. These results showed that a combination of Treg cell-depletion using anti-CD25 mAbs and CTL administration is a feasible approach for treatment of cancers which warrants further exploration in the clinical setting.

Depletion of CD4+CD25high regulatory T cells from tumor infiltrating lymphocytes predominantly induces Th1 type immune response in vivo which inhibits tumor growth in adoptive immunotherapy

“…21,22 However, the efficacy of adoptive transfer of TILs is limited. 23,24 One important factor is bulk TILs are heterogeneous, which contain various lymphocyte subsets with different immune functions. Some of the subsets such as Treg participate in tumor-induced immune suppression.…”

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

“…Recent studies have reported that the increased number of Treg cells in the peripheral blood and TILs in patients with ovarian, gastric or esophageal cancer could impair cell-mediated immunity and promote disease progression (Morse et al, 2008). Previous studies have demonstrated that removing or suppressing Treg cells can strengthen antitumor immunity (Ohmura et al, 2008;Setiady et al, 2010), and these studies indicate that Treg cells play a negative regulatory role in human antitumor immunity. In our study, we showed an increased numbers of CD4+CD25+Foxp3+ T cells in the TILs of HCC, which are inconsistence with previous results.…”

Cryptotanshinone Induces Inhibition of Breast Tumor Growth by Cytotoxic CD4+ T Cells through the JAK2/STAT4/ Perforin Pathway

“…Considered that tumorreactive Cytotoxic CD4+ T cells have been a bright point in immunotherapy of tumor (Porakishvili et al, 2001;Quezada et al, 2010;Akhmetzyanova et al, 2013), so we also measured perforin production of CD8+ T cells as well as CD4+ T cells. Unfortunately, CPT showed marginal effect on CD8+ cytotoxic T cells, even though that CD8+ cytotoxic T cells are classic tumor killing cells (Ohmura et al, 2008), but enhanced perforin production of CD4+ T cells. To further verify this result, we isolated CD4+ and CD8+ T cells from tumor-bearing mice and analyzed their cytotoxic ability, results same with in vivo data.…”