2.2.3. Specific Targeting

Furthermore, the incorporation of biological substances into source tumor cells could also augment TCL-mediated immune activation. One of these stimulatory substances is known to act as an agonist peptide to activate CD47 in cancer cells. Previous reports demonstrated that CD47 activation using soluble peptides derived from thrombospondin-1(TSP-1) effectively induced cell death in several types of cancer cells (Figure 2F) [48,49]. Particularly, ICD induced by a TSP1-derived CD47 agonist (PKHB1 peptide: KRFYVVMWKK), and DC activation using TCLs obtained from PKHB1-treated L5178YR tumor cells (PKHB1-TCL), has been reported [33]. The sequential mechanisms of (1) CD47 activation by PKHB1, (2) exposure to several DAMPs by atypical caspase-independent and calcium-dependent signaling in cell death, (3) the enhanced maturation of bone marrow-derived DCs with

proper antigen presentation, and (4) the stimulation of antitumor T cell responses in an in vivo L5178Y-R tumor model using syngeneic BALB/c mice, were obtained using PKHB1 TCLs.
