Rabbit Anti-Human CD70 (a.a. 39-193) Polyclonal antibody

Purpose Successful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen-presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell-based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals. Materials and Methods Antigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax). Results T cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization. Conclusion These results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.

Various cell types can produce the chemokine CXCL10 in response to IFN-gamma stimulation. CXCL10 is generally viewed as a proinflammatory chemokine that promotes recruitment of CD8(+) and Th1-type CD4(+) effector T cells to infected or inflamed nonlymphoid tissues. We show that CXCL10 plays a role during CD8(+) T cell priming in the mouse. Genome-wide expression profiling revealed the Cxcl10 gene as a target of CD27/CD70 costimulation in newly activated CD8(+) T cells. CD27/CD70 costimulation is known to promote activated T cell survival, but CXCL10 did not affect survival or proliferation of primed CD8(+) T cells in vitro. Accordingly, CXCL10 could not fully rescue CD27 deficiency in mice infected with influenza virus. Rather, CXCL10 acted as chemoattractant for other activated CD8(+) T cells. It signaled downstream of CD27 in a paracrine fashion to promote generation of the CD8(+) effector T cell pool in the Ag-draining lymph nodes. Consistently, CD8(+) T cells required expression of the CXCL10 receptor CXCR3 for their clonal expansion in a CD27/CD70-dependent peptide-immunization model. Our findings indicate that CXCL10, produced by primed CD8(+) T cells in response to CD27/CD70 costimulation, signals to other primed CD8(+) T cells in the lymph node microenvironment to facilitate their participation in the CD8(+) effector T cell pool.