![]() ![]() Transduction of the CLL-cell-line MEC1 to express ROR1 enhanced expression of target genes induced by ROR1-signaling, increased expression of BCL-XL, and enhanced resistance to venetoclax, even in MEC1 made to express mutant forms of BCL2, which are associated with venetoclax resistance. At SC2, we also observed upregulation of genes induced by Wnt5a-induced ROR1 signaling, including BCL2L1. By examining the CLL cells from such patients prior to therapy at SC1 and then more than 1 year later (Sample Collection 2 (SC2)), when they had progressive increases in MRD despite continued venetoclax therapy, we found the levels of ROR1 expressed on CLL cells at SC2 were significantly higher than that on CLL cells collected at SC1. We examined the CLL cells of seven such patients (CLL1-7) and found each had high-level expression of ROR1. Philadelphia (PA): AACR Cancer Res 2023 83(8_Suppl):Abstract nr LB218.Although the BH3-mimetic venetoclax is highly cytotoxic for chronic lymphocytic leukemia (CLL) cells, some patients with CLL fail to clear minimal residual disease (MRD). In: Proceedings of the American Association for Cancer Research Annual Meeting 2023 Part 2 (Clinical Trials and Late-Breaking Research) 2023 Apr 14-19 Orlando, FL. Developing a bispecific anti-ROR1 antibody drug conjugate for hematological and solid tumor treatment. The lead candidate molecule, BR111A will start the preclinical studies soon.Ĭitation Format: Xiaobei Zhao, Jie Zhu, Zhenhua Wu, Jing Li, yaqiong zhou, Lei Nie, Gang Chen. In vitro and In vivo studies demonstrated the antitumor activity of anti-ROR1 ADCs outperformed the lead anti-ROR1 ADC currently in phase II/IIl trial, providing a promising treatment for hematological and solid cancers with a better safety profile and a larger therapeutic window. Our novel linker structure prevents payloads from coming off of the antibody during the circulation, significantly reduced the off-target toxicity. The bispecific mAbs that target to two different epitopes of ROR1, are superior to those antibodies that target to single epitope in the binding to ROR1-expressing tumor cells, the induction of tumor cell death and anti-tumor immunity. Those unique ADCs consist of a humanized monoclonal antibody (mAb against single epitope) or a bispecific antibody (BsAb against two epitopes), stably conjugated to an antimitotic agent. Utilizing our unique and innovated linker platform, we screened many anti-ROR1 ADCs, with defined DAR=4. ![]() The current clinical results of ROR1 ADC have been promising in treating patients with relapsed and/or refractory (R/R) hematologic malignancies. Although being an oncofetal protein with limited expression in most of the normal tissues, ROR1 is expressed abnormally in various hematological and solid cancers, making it a highly attractive target for antibody-drug conjugate (ADC) therapy. It is also involved in the development and progression of many types of cancer. ROR1 is a receptor for Wnt family signaling molecules Wnt5a and is a key regulator of normal cellular process, including cell proliferation, survival, and migration. Receptor tyrosine kinase ROR1 is a type I transmembrane protein belongs to the ROR family members. ![]() Developing a bispecific anti-ROR1 Antibody Drug Conjugate for hematological and solid tumor treatment ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |