GPC3-targeted therapeutic agent for administration to patients for whom GPC3-targeted therapeutic agent therapy is effective
A technology targeting therapeutic agents and patients, applied to medical preparations containing active ingredients, antibody medical ingredients, chemical instruments and methods, etc., can solve problems such as ignorance
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[0195] (1) Preparation of effector cells
[0196] Spleen cells were isolated from spleens excised from CBA / N mice or the like in RPMI1640 medium (Invitrogen). Wash the spleen cells obtained with the above medium containing 10% fetal bovine serum (FBS, HyClone), and adjust the concentration of the cleaned spleen cells to 5×10 6 cells / mL, and thus the effector cells can be prepared.
[0197] (2) Preparation of complement solution
[0198] A complement solution was prepared by diluting Baby Rabbit Complement (CEDARLANE) 10-fold with a medium (Invitrogen) containing 10% FBS.
[0199] (3) Preparation of target cells
[0200] In DMEM medium containing 10% FBS, the cells expressing the antigen were mixed with 0.2mCi 51 The target cells were radiolabeled by incubating with Cr-sodium chromate (GE Healthcare Life Sciences) for 1 hour at 37°C. After radiolabeling, wash 3 times with RPMI1640 medium containing 10% FBS, and adjust the concentration of washed cells to 2×10 5 cells / mL, ...
Embodiment 1
[0442] GC33 (common name: codrituzumab) used in this example is a genetically recombinant humanized IgG1 monoclonal antibody capable of binding to human GPC3 with high affinity (WO2006 / 006693). To confirm GC33 in patients with progressive and / or recurrent hepatocellular carcinoma (HCC) who progressed after full treatment with at least 1 dose of systemic therapy, or whose administration was discontinued due to adverse events, unresectable The effect in patients with progressive or metastatic hepatocellular carcinoma, a multi-center joint randomized double-blind trial placebo-controlled phase II clinical trial (NP-27884 trial). The main purpose is to evaluate the effectiveness based on the progression-free survival period of patients with progressive or metastatic HCC, and to evaluate the effectiveness of the overall survival, disease control rate, and progression-free period as indicators, as well as safety and / or resistance. In this study, where the evaluation of the acceptabi...
Embodiment 2
[0448] When PFS events were obtained in 128 cases out of 121 cases administered with GC33 as described above and 60 cases administered with placebo, the effect of administration of GC33 in GPC3-targeted therapy was evaluated using PFS. In addition, as a secondary evaluation, evaluation was performed using OS when the overall survival (OS) reached 92 events. As a result, neither PFS nor OS was seen to prolong the effect brought about by GC33 administration ( figure 1 ). In addition, in the evaluation of each GPC3-IHC score (composite evaluation score 2), no prolongation effect was observed in any of the scores.
[0449] In addition, for the GC33 administration group, the population PK model obtained using the GC33 serum concentration value in this phase II clinical trial was used to estimate the blood concentration before administration on the 3rd cycle and the 1st day (4th week from the start of the initial administration). The bottom value of GC33 was cut-off at 230 μg / ml, ...
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