On November 9, 2019 Bolt Biotherapeutics, Inc., a private biotechnology company focused on using its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to unleash the power of the immune system to treat cancer, reported new preclinical data demonstrating profound antitumor efficacy for its lead HER2 ISAC therapeutic program, when administered as a monotherapy, resulting in the complete eradication of large tumors (Press release, Bolt Biotherapeutics, NOV 9, 2019, View Source [SID1234550864]). The poster presentation entitled "HER2-targeting TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation and anti-tumor immune responses in a TLR- and FcR- dependent manner" was presented at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in National Harbor, Maryland.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"These exciting preclinical data provide a strong rationale for moving our ISAC cancer immunotherapy platform into clinical testing and I’m pleased to report that we expect to initiate our first clinical trial for our HER2 monotherapy in early 2020," stated Randall Schatzman, Ph.D., chief executive officer of Bolt. "While much progress has been made in cancer immunotherapy, there still remains a significant need for single-agent therapies that can impact well-established tumors and provide durable efficacy in tumors that are refractory to standard of care therapies. Our proprietary Boltbody ISACs embody all of these components, and we are highly optimistic about the future of this platform to impact cancer."
"We believe such profound antitumor activity is unprecedented, including complete tumor eradication in large tumors, with an immunotherapeutic systemically administered as a monotherapy," stated David Dornan, Ph.D., senior vice president of research at Bolt Biotherapeutics. "Our data define the details of the mechanism of action by which our Boltbody technology is able to eliminate these hard to treat solid tumors, while generating immunological memory to suppress recurrence."
In the series of studies presented at SITC (Free SITC Whitepaper), key preclinical data show:
ISAC antitumor activity requires tumor target expression, interaction with Fc gamma receptors on immune cells, and TLR7/8 engagement
Single-agent anti-HER2 ISAC treatment led to in vivo tumor regression and clearance in models with large tumor burden and are resistant to anti-HER2 naked antibody treatment
Immunological memory was achieved as measured by protection from subsequent tumor growth. In syngeneic tumor models in which anti-HER2 ISAC treatment led to tumor clearance, hosts that were re-challenged with the parental tumor cell line lacking HER2 antigen expression were resistant to tumor growth. This protection was mediated by T cells as evidenced by the ability to re-establish tumors after the deletion of CD4 and CD8 T cells.
About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of innate immune agonists to convert cold tumors into immunologically hot tumors thereby illuminating tumors to the immune system and allowing them to be invaded by tumor killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.