WEITAO ZHENG¹, DONG JIANG², SONGEN CHEN¹, MEILING WU¹, BAOQI YAN², JIAHUI ZHAI², YUNQIANG SHI², BIN XIE¹, XINGWANG XIE², KANGHONG HU^1,*, WENXUE MA^3,*

Oncology Research, Vol.32, No.12, pp. 1837-1850, 2024, DOI:10.32604/or.2024.056565 - 13 November 2024

Abstract Objectives: The Kirsten rat sarcoma virus (KRAS) G12D oncogenic mutation poses a significant challenge in treating solid tumors due to the lack of specific and effective therapeutic interventions. This study aims to explore innovative approaches in T cell receptor (TCR) engineering and characterization to target the KRAS G12D_7-16 mutation, providing potential strategies for overcoming this therapeutic challenge. Methods: In this innovative study, we engineered and characterized two T cell receptors (TCRs), KDA11-01 and KDA11-02 with high affinity for the KRAS G12D_7-16 mutation. These TCRs were isolated from tumor-infiltrating lymphocytes (TILs) derived from tumor tissues of patients More >

GERHARD HAMILTON^*, MARIE-THERESE EGGERSTORFER, SANDRA STICKLER

Oncology Research, Vol.32, No.8, pp. 1257-1264, 2024, DOI:10.32604/or.2024.051653 - 17 July 2024

Abstract The Kirsten rat sarcoma virus—son of sevenless 1 (KRAS-SOS1) axis drives tumor growth preferentially in pancreatic, colon, and lung cancer. Now, KRAS G12C mutated tumors can be successfully treated with inhibitors that covalently block the cysteine of the switch II binding pocket of KRAS. However, the range of other KRAS mutations is not amenable to treatment and the G12C-directed agents Sotorasib and Adragrasib show a response rate of only approximately 40%, lasting for a mean period of 8 months. One approach to increase the efficacy of inhibitors is their inclusion into proteolysis-targeting chimeras (PROTACs), which… More > Graphic Abstract