On August 7, 2024 Agenus Inc. (NASDAQ: AGEN), a leader in developing novel immunological agents to treat various cancers, reported the publication of a seminal study in the prestigious Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), detailing the novel mechanism of action and effectiveness of botensilimab, an investigational, novel multifunctional anti-CTLA-4 antibody, in various treatment-resistant cancers (Press release, Agenus, AUG 7, 2024, View Source [SID1234645521]).
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The paper, entitled "Botensilimab, an Fc-Enhanced Anti-CTLA-4 Antibody, Is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy," highlights several key findings:
Demonstrated Activity Across Multiple Cancers: Botensilimab has shown increased activity in multiple treatment-resistant cancers, including those that have progressed on prior checkpoint inhibitors.
Fc-Enhanced Design for Multifunctional Immune Activation: Unlike traditional anti-CTLA-4 antibodies, botensilimab’s Fc-enhanced design allows it to leverage multiple immune-activating mechanisms simultaneously. This includes enhanced T cell priming, reduction of intratumoral regulatory T cells, and activation of antigen-presenting cells, leading to a robust anti-tumor response.
Activity Independent of Conventional Limitations: Botensilimab shows clinical activity regardless of factors that typically limit conventional immunotherapy efficacy, such as tumor neoantigen burden and FcγRIIIA genotype. This broadens its potential applicability across diverse patient populations.
Remodeling the Tumor Microenvironment: The antibody uniquely remodels the tumor microenvironment, transforming "cold" tumors that are currently unresponsive to immune therapies into "hot" immunologically active tumors. This is achieved by reducing regulatory T cells and increasing T cell inflammation gene signatures within the tumor microenvironment.
Promise in Difficult-to-Treat Cancers: Botensilimab demonstrates significant promise in treating over nine difficult-to-treat cancers, including microsatellite stable colorectal cancer and may extend clinical benefits to patient populations historically unresponsive to conventional immune checkpoint inhibitors.
"We are thrilled to share these groundbreaking findings with the scientific community," said Dhan Chand, PhD, lead author and Vice President of Research at Agenus. "The compelling preclinical and clinical evidence generated with botensilimab reveal an actionable pathway to improve treatment outcomes and extend survival to patient populations historically unresponsive to conventional immune checkpoint inhibitors."
This paper underscores the potential of botensilimab to overcome some of the most challenging hurdles in cancer treatment, offering new hope to patients with limited options. Agenus is committed to advancing this promising therapy through further clinical development and regulatory pathways to ensure rapid and broad patient access.
About Cancer Discovery
Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials. As the premier cancer information resource, the Journal also presents Review Articles, Perspectives and Commentaries, News stories, and Research Watch summaries of important journal articles to its readers to keep them informed about the latest findings in the field. Topics span the spectrum of cancer research and medicine from the laboratory to the clinic and epidemiologic studies.
About Botensilimab
Botensilimab is an investigational human Fc-enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.