CAR-NK program

01. Industrializing Off-the-Shelf Cell Line-based Therapies

02. Cell Engineering Platforms: viral & non-viral

Diverse genetic engineering technologies to harness the power of cell lines

03. A novel NK cell line platform, NK101

^†NK101 is a clonal cell line derived from a patient with extranodal NK/T cell lymphoma

● Features of CD56^dimCD62L⁺ polyfunctional NK subset at the middle stage of maturation
● Distinct immunostimulatory and proliferative potentials

04. NK cell platforms in the field: competitive analysis

NK cell lines provide genuine “off-the-shelf” therapeutics w/ “industrial scalability”

● iPSC, inducible pluripotent stem cells; GE, genetic engineering; CRS, cytokine release syndrome; GVHD, graft versus host disease

05. NK cell lines in the field: competitive analysis

NK101 demonstrates the best-in-class scalability & immunostimulatory potential
NK101 provides the most robust platform for multifunctional genetic engineering

● CAR, chimeric antigen receptor; IL-2, interleukin 2; TRAIL, TNF-related apoptosis inducing ligand; HLA, human leukocyte antigen

06. 1^st generation engineering approach for NK101

● DN, dominant negative; mb, membrane bound; CD, cytosine deaminase; TME, tumor microenvironment

07. 2^nd generation engineering approach for NK101

● mAb, monoclonal antibody; KO, knockout; sc, single chain; TK, thymidine kinase; GCV, ganciclovir; tEGFR, truncated epidermal growth factor receptor

08. 2^nd generation engineering approach for NK101

Universal & off-the-shelf NK cell therapeutics optimized for mAb combination

● ^†Discovery of a novel natural killer cell line with distinct immunostimulatory and proliferative potential as an alternative platform for cancer immunotherapy. Journal for ImmunoTherapy of Cancer 2019; 7(1):138.; Novel natural killer cell line and use thereof. KR102081987 B1
● HLA, human leukocyte antigen; KO, knockout; CAR, chimeric antigen receptor; mAb, monoclonal antibody; TRAIL, TNF-related apoptosis inducing ligand; CD, cytosine deaminase; 5-FC, 5-fluorocytosine; 5-FU, 5-fluorouracil; ha, high-affinity

09. NK104: HLA-edited, CD16V-CAR modified NK101

Potential applications of NK103

● Screening therapeutic mAbs for ADCC responsiveness
● Quality control or lot release testing of therapeutic mAbs for ADCC responsiveness
● Therapeutic use: injection of irradiated NK103 in combination with therapeutic mAbs to boost ADCC responses

● CAR, chimeric antigen receptor; HLA, human leukocyte antigen; ha, high affinity