Organic Seminar – Oscar Hernandez
About the event
Organic Seminar, 3/3/2026, 12:30 PM, Fulmer 438
Speaker: Oscar Hernandez
Group: Dr. Cliff Berkman
Title: A HER2-targeting antibody-MMAE conjugate RC48 sensitizes immunotherapy in HER2-positive colon cancer by triggering the cGAS-STING pathway
Abstract
This presentation will focus on the work conducted by Dr. Xiaohan Wu’s group which focuses on targeted drug therapy for HER2 expressing colon cancer. Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Herein Dr. Wu’s group found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2- positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of this study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.
References
Wu X, Xu L, Li X, Zhou Y, Han X, Zhang W, Wang W, Guo W, Liu W, Xu Q, Gu Y. A HER2-targeting antibody-MMAE conjugate RC48 sensitizes immunotherapy in HER2-positive colon cancer by triggering the cGAS-STING pathway. Cell Death Dis. 2023 Aug 24;14(8):550. doi: 10.1038/s41419-023-06073-8. PMID: 37620320; PMCID: PMC10449775.