B7-H3 (CD276): A potential next-generation novel target for treatment-resistant cancer
Sep 08, 2022 | DelveInsight
Significant treatment advances in a variety of tumor types, including melanoma, NSCLC, bladder, and kidney cancers, among others, have been made possible by immune-checkpoint inhibitors. Immune-checkpoint inhibitors, however, have a terrible record in treating certain cancers. Hence, it becomes important to come up with advanced or next-generation immunotherapy options. B7-H3 (CD276) has been shown to have immunomodulatory characteristics. B7-H3 is an immunomodulatory transmembrane N-linked glycoprotein that is overexpressed in solid tumors including small cell lung cancer, NSCLC, breast cancer, and others. As a result of the success of immune checkpoint inhibitors (ICIs) in cancer immunotherapy, B7-H3, a member of the same protein family as PD-L1, has attracted attention as one of several potential targets. At present, there is considerable interest in developing combination therapies to improve response rates and outcomes in cancer patients.
An update of the extended follow-up of DS-7300 from its Phase I/II trial conducted on patients with advanced solid tumors cannot be overlooked at the upcoming ESMO 2022. DS-7300 is an investigational B7-H3-directed ADC and is one of five ADCs currently in clinical development in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to several topoisomerases I inhibitor payloads (an exit can derivative, DXd) via tetrapeptide based cleavable linkers.
Data presented at the ESMO 2021 virtual congress showed promising early clinical activity in patients with several types of advanced solid tumors. Subsequently, preliminary results from the metastatic castration-resistant prostate cancer (mCRPC) patient subset were presented at ASCO 2022 Genitourinary Cancers Symposium. DS-7300 was well tolerated with an acceptable safety profile in patients with mCRPC. Preliminary data indicated improvements in prostate-specific antigen (PSA) and bone metastases. In contrast to B7-H3, CTLA-4 and PD-L1 are infrequently seen in prostate cancer. Scientists have discovered that almost all prostate cancer cells contain some B7-H3, which seems to be linked to more rapid recurrence and early metastasis. A possible novel target for treatment-resistant prostate cancer is B7-H3. The company is also intending to present another abstract at ESMO 2022 (1550TiP; Extensive-stage small cell lung cancer)
Currently, no B7-H3 directed medicines have been approved in oncology. It will be intriguing to see if DS-7300 continues to demonstrate promising clinical activity and emerge as a pipeline frontrunner for Daiichi. Apart from Daiichi, Xencor, MacroGenics, Y-mAbs Therapeutics, BioAtla, Fate Therapeutics, AbbVie, GT Biopharma, and others, are attempting to utilize the B3-H7 immune checkpoint in oncology.