C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity

Abstract

(2015) C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity, mAbs, 7:2, 321-330,

Use of Single-Chain Antibody Derivatives for Targeted Drug Delivery

“…To examine whether CLL1:TRAIL synergizes the anticancer effect of monoclonal antibodies, they co-treated FaDu (EGFR-expressing cells) and Ramos B cells (CD20-expressing cells) with CLL1:TRAIL-armed granulocytes and a relevant monoclonal antibody (cetuximab and rituximab, respectively). In both cases, apoptosis was increased significantly, indicating a potential role of antibody-dependent cell-mediated cytotoxicity in synergizing the anticancer activity of CLL1:TRAIL (47).…”

“…Phagocytes express a surface antigen, called C-type lectin-like molecule-1 (CLL1), which can be exploited for targeted drug delivery to these cells. Wiersma and colleagues produced a fusion peptide composed of an anti-CLL1-scFv and sTRAIL to specifically deliver TRAIL to granulocytes (47). They found that the fusion peptide, called CLL1:TRAIL, was able to specifically bind to and increase the antitumor activity of granulocytes.…”

Correlation between Polymorphism of TRAIL Gene and Condition of Intervertebral Disc Degeneration

“…Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily and plays a specific role in the induction of tumor cell apoptosis, but without any significant effects on normal tissues [ 3 – 5 ]. Currently there are few studies regarding the genetic regulation of TRAIL and IDD.…”

Programmed Death Ligand 1 (PD-L1)-targeted TRAIL combines PD-L1-mediated checkpoint inhibition with TRAIL-mediated apoptosis induction

“…4,5 Previously, we demonstrated that direct arming of myeloid effector cells using a TRAIL fusion protein that binds to CLL-1 on granulocytes, enhanced the pro-apoptotic activity of such myeloid cells. 26 To assess whether potentiation of myeloid effector cell activity might also contribute to anti-PD-L1:TRAIL activity, we generated various myeloid effector cell populations, i.e., monocytes, M0, M1, and M2 macrophages, iDCs and mDCs. All of these effector cells expressed PD-L1 to a varying degree, with monocytes having lowest and mDCs having the highest expression (Fig.…”

“…24 Furthermore, scFv-mediated display of TRAIL on the surface of T cells or granulocytes augments the cytolytic activity of these immune effector cells. 25,26 Based on this bi-functional TRAIL-based fusion protein format, we constructed and pre-clinically evaluated an anti-PD-L1:TRAIL fusion protein comprised of a PD-L1-blocking antibody fragment genetically fused to human soluble TRAIL. This anti-PD-L1:TRAIL fusion protein was designed to combine PD-L1 checkpoint inhibition with simultaneous TRAIL-mediated activation of cancer cell death.…”