AACR (American Association for Cancer Research) Annual Meeting 2021: ePoster submission

<Abstract>

To achieve successful anti-cancer response with IL-2, it is necessary to develop a method delivering selective IL-2 signaling on CD8 T and NK cells than Tregs We report preclinical results with SLC-3010 that consist of IL-2 conjugate with anti-IL-2 antibody named TCB2 TCB2 is a humanized mouse antibody that specifically recognize the epitope on IL-2 where interact with CD25 as demonstrated with crystallography To develop SLC-3010, stable cell lines producing wild type human IL-2 or TCB2 were separately manufactured using mammalian cell system The pharmacokinetics analysis of SLC-3010 revealed 8-12h of half-life in mouse Although SLC-3010 dose not employ any artificial linker between IL-2 and TCB2, the half-life of SLC-3010 is comparable with other IL-2 based molecules thereby demonstrating stable binding of TCB2 against IL-2 under physiological condition In mouse model, single dosing of SLC-3010 preferentially stimulates CD8 T cells than Tregs in both secondary lymphoid organ and tumor microenvironment SLC-3010 exhibited strong anti-tumor activity which is demonstrated with circulating B cell lymphoma, metastatic solid tumor, and traditional solid tumor models Furthermore, synergistic anti-tumor response was observed by SLC-3010 with various anti-cancer drugs including chemotherapeutic reagents, targeted therapeutics, and checkpoint inhibitors such as anti PD-1 and anti CTLA-4 Once the transplanted tumor was completely cured by SLC-3010, the mice acquired strong memory response against the rejected tumor indicating strong immunological memory formation against recurrent tumors Non-human primate (NHP) efficacy test revealed that single dosing of SLC-3010 expanded CD8 T and NK cells in dose dependent manner, hence the number of CD8 T cells were increased up to 5 fold in the PBMC population with non-toxic dose of SLC3010 The peak of response in NHP was day 6-7 as analyzed the number of CD8 T cells in PBMC The strong activation of CD8 and NK cells with NHP model indicating that the binding of TCB2 and IL-2 is stable in the system as well The SLC-3010 induced selective stimulation of CD8 T cells was also demonstrated with human T cells using humanized NSG mice thereby providing an insight for developing future clinical trials with SLC-3010.