Immunotherapy Drug Eliminates Aggressive Cancers in Clinical Trial Date: August 14, 2025 Source: The Rockefeller University News --- Overview A novel immunotherapy drug, engineered by Rockefeller scientists, shows remarkable promise in eliminating aggressive cancers. The drug, a CD40 agonist antibody called 2141-V11, was tested in a phase 1 clinical trial with notable results: 12 patients with various metastatic cancers participated (melanoma, renal cell carcinoma, breast cancer) 6 patients experienced tumor shrinkage 2 patients achieved complete remission (tumors disappeared entirely) This research was published in Cancer Cell and led by Jeffrey V. Ravetch’s lab in collaboration with Memorial Sloan Kettering Cancer Center. --- Background CD40 agonist antibodies activate the immune system to attack cancer cells. Historically, these drugs showed success in animal models but limited patient efficacy and caused severe side effects such as systemic inflammation, low platelets, and liver toxicity. Ravetch’s 2018 work engineered an enhanced CD40 agonist antibody (2141-V11) with improved efficacy and reduced toxicity by modifying its Fc region and changing administration to direct intratumoral injection rather than intravenous. --- Clinical Trial Highlights The drug is 10x more potent in triggering antitumor immunity in preclinical models. Intratumoral injection significantly limited systemic toxicities. Patients treated had a variety of aggressive metastatic cancers. Remarkable systemic responses included shrinkage or disappearance of tumors distant from the injection site. Two patients (one with melanoma, one with breast cancer) had all metastatic tumors vanish after treatment focused on just one tumor. --- Mechanism of Action CD40 is a receptor triggering immune activation and fostering tumor-specific T cell responses. The drug induced the formation of tertiary lymphoid structures (TLS) in tumors—immune cell aggregates resembling lymph nodes. TLS presence is associated with improved immunotherapy outcomes. Immune activation extended to non-injected tumor sites, indicating robust systemic immunity induction. --- Implications & Future Research This trial has sparked further phase 1 & 2 clinical studies at Rockefeller, Memorial Sloan Kettering, and Duke University. Studies will focus on: Cancers such as bladder cancer, prostate cancer, glioblastoma. Identifying markers predicting patient response to therapy. Turning non-responders into responders. Early data suggest a need for a pre-existing immune environment with high T cell clonality for optimal drug efficacy. --- Key Takeaways Rockefeller scientists have developed an enhanced CD40 agonist antibody with greater efficacy and fewer side effects. Phase 1 clinical trial of 2141-V11 shows tumor shrinkage in half of the patients and complete remission in some. The drug induces systemic antitumor immunity after local injection. Ongoing trials aim to broaden cancer types treated and understand patient response mechanisms. --- Additional Information Lead Researcher: Jeffrey V. Ravetch Published Article: Osorio et al., Cancer Cell (DOI: 10.1016/j.ccell.2025.07.013) Media Contact: Katherine Fenz, Media Relations Manager, kfenz@rockefeller.edu, 212-327-7913 --- Related Topics at Rockefeller University Research across 72 biomedical laboratories. Extensive education and training programs. Support opportunities and philanthropy. Events & lectures featuring leading experts. --- For continuous updates and more information on cancer immunotherapy and related science, subscribe to Rockefeller University's newsletter or follow their social channels.