Historically, Immuno-oncology has focused on T cell-driven effects. However, a growing class of myeloid therapies including immune-stimulating antibody conjugates or ISACs, which comprise a tumor-targeting antibody conjugated to an immune-stimulating payload, are under investigation. TLR-activating ISACs require both tumor-associated antigens and tumor-resident myeloid cells for activity.
With the development of novel IO strategies, a proper understanding of the myeloid landscape is relevant for cancer biology and drug development.
During the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, being held at McCormick Place in Chicago and virtually from June 3-7, 2022 will, research will be presented that demonstrates that myeloid cells are consistently present in solid tumors.
“Based on the data we believe myeloid cells represent an attractive cellular target to address cancer more broadly,” noted Edith A. Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics.
“Myeloid cells are key cell types that serve as immunologic sentinels within the tumor microenvironment and can directly kill tumor cells or activate long-lasting cytotoxic T cells,” she added.
“Myeloid-targeted therapies, as single-agents or in combination with approved therapies, have the potential to benefit patients who may or may not have previously benefited from T cell-targeted approaches.”
This approach is being developed by Bolt Biotherapeutics, a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems.
Bolt Biotherapeutics is currently developing a pipeline of myeloid-targeting therapies, including immune-stimulating antibody conjugates (ISACs) and BDC-3042 (a Dectin-2 agonistic antibody), designed to kill tumors through activation of myeloid cells and subsequent recruitment of T-cells.
The data demonstrate that myeloid cells are present in all tested tumor microenvironments, including those with low T-cell infiltration. These findings support the potential for myeloid-directed therapies to activate the innate immune system as a bridge to adaptive immunity, including in patient populations who have demonstrated resistance to T cell-mediated immune checkpoint blockade. The data also validate the tumor cell expression of tumor antigens HER2, CEA, and PD-L1, all of which are targets of Boltbody™ ISAC candidates.
Blum LK, Ptacek J, LeBlanc H, Mallet WG, Hug BA, Alonso MN, Perez EA, Dornan D, Kowanetz M. Characterization of tumor antigen expression and myeloid immune profiles to inform the development of immune stimulating antibody conjugates (ISACs). Journal of Clinical Oncology 2022 40:16_suppl, 2557-2557 | DOI: 10.1200/JCO.2022.40.16_suppl.2557 / Poster 212 [Article]
Featured image: Featured Image: Attendees listen during the plenary session of the 2017 Annual Meeting of the American Society of Clinical Oncology in Chicago, Ill. Courtesy: © 2017 ASCO/Todd Buchanan. Used with permission.