AI Article Synopsis
- Immunocytokines, like KD033, combine an antitumor antibody with an immune-activating cytokine to target and activate the immune response in cancer's immunosuppressive environment.
- A surrogate version of KD033 (srKD033) demonstrated strong antitumor effects and durable immunity in mouse models, particularly in colon tumors, by promoting the expansion of cytotoxic immune cells.
- The srKD033 treatment was well-tolerated and showed significant effectiveness against tumors resistant to standard therapies, highlighting its potential as a promising cancer treatment option.
Article Abstract
Immunocytokines hold great potential as anticancer agents, as they use a specific antitumor antibody to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME). We have developed a novel immunocytokine (KD033) composed of a fully human, high-affinity antiprogrammed death-ligand 1 (PD-L1) linked to the sushi-domain of the human IL-15/IL-15 receptor alpha (IL-15/IL-15Rα) complex. A murine PD-L1 cross-reactive KD033 surrogate (srKD033) and a nontargeting antibody (ntKD033) were also developed to investigate mechanism of action in murine tumor models. Efficacy analyses showed a robust antitumor effect of single-dose srKD033 in several diverse syngeneic murine tumor models. In a CT26 murine colon tumor model, single-dose srKD033 produced durable antitumor immunity as evidenced by resistance to subsequent tumor rechallenges. Mice responding to srKD033 treatment showed increased retention of PD-L1/IL-15 in the TME which likely facilitated prolonged IL-15-induced expansion of cytotoxic cells. Importantly, target-based PD-L1/IL-15 delivery via srKD033 was well-tolerated and induced significant antitumor activity in murine carcinoma models that are non- or minimally responsive to IL-15 or anti-PD-L1/PD-1 monotherapy.
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| http://dx.doi.org/10.1158/1535-7163.MCT-20-0457 | DOI Listing |
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