The majority of the current immunotherapy approaches are focused on the adaptive immune response. Bolt is seeking to successfully engage the innate immune system that will ultimately trigger the adaptive immune system to generate a robust anti-tumor immune response.
Myeloid cells are a group of immune cells that belong to the innate immune system, consisting of cell types known as monocytes, macrophages, dendritic cells, and granulocytes. These cells serve various essential roles in the body’s immune system. They are critically involved in the regulation of T cell responses, bridging our body’s innate and adaptive immune systems. Due to various immunosuppressive factors produced in the tumor microenvironment, the normal function of these cells can be inhibited, limiting their ability to create a productive anti-tumor immune response.
When functioning properly, myeloid cells can stimulate anti-tumor effects in the body, including direct tumor cell killing as well as activation of tumor-specific T cells to support durable anti-tumor immune responses and immunological memory. Activated myeloid cells also secrete pro-inflammatory chemokines and cytokines that recruit additional immune effector cells and help convert immunologically “cold” tumors into “hot” tumors. As such, these normally tumor-supportive myeloid cells can be converted to tumor-destructive myeloid cells that amplify innate and adaptive immune responses, leading to productive anti-tumor immunity.
Our Boltbody immune-stimulating antibody conjugate (ISAC) approach is pioneering a new category of immunotherapies that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. By activating and recruiting myeloid cells, Boltbody ISACs re-program the tumor microenvironment to invoke a new anti-tumor immune response.
Our Boltbody ISACs are delivered systemically but act locally in the tumor microenvironment by triggering a localized anti-tumor immune cascade. This process enables the patients’ own immune system to determine which are the relevant T cells to mobilize for tumor destruction and subsequent immunosurveillance, demonstrating how an off-the shelf Boltbody immunotherapeutic can deliver a personalized therapeutic outcome. We believe that the development of systemic immunological memory will result in long-term anti-tumor responses.
Unlike immuno-oncology approaches that seek solely to relieve immune suppression, Boltbody ISACs act by reengaging the immune system to become an active participant in the cancer immune cycle. The following key features provide us with the opportunity for robust applications across various solid tumors designed to deliver potent, safe, and durable therapeutics:
We designed our Boltbody ISACs with three primary components: a tumor antigen-targeting antibody, a linker that can be designed either as cleavable or non-cleavable, and a proprietary immune stimulant to activate the patient’s innate and adaptive immune system. Together these components allow our Boltbody ISACs to overcome the limitations of existing immunotherapies by triggering both the body’s innate and adaptive immune systems through different stages of the cancer immunity cycle to produce long-term anti-tumor activity.
Our Boltbody immune stimulating antibody conjugate (ISAC) approach is pioneering a new category of immunotherapies that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. By activating and recruiting myeloid cells, Boltbody ISACs re-program the tumor microenvironment to invoke a new anti-tumor immune response.
Our Boltbody ISACs are delivered systemically but act locally in the tumor microenvironment by triggering a localized anti-tumor immune cascade. This process enables the patients’ own immune system to determine which are the relevant T cells to mobilize for tumor destruction and subsequent immunosurveillance, demonstrating how an off-the shelf Boltbody immunotherapeutic can deliver a personalized therapeutic outcome. We believe that the development of systemic immunological memory will result in long-term anti-tumor responses.
Unlike immuno-oncology approaches that seek solely to relieve immune suppression, Boltbody ISACs act by reengaging the immune system to become an active participant in the cancer immune cycle. The following key features provide us with the opportunity for robust applications across various solid tumors designed to deliver potent, safe, and durable therapeutics:
We designed our Boltbody ISACs with three primary components: a tumor antigen-targeting antibody, a linker that can be designed either as cleavable or non-cleavable, and a proprietary immune stimulant to activate the patient’s innate and adaptive immune system. Together these components allow our Boltbody ISACs to overcome the limitations of existing immunotherapies by triggering both the body’s innate and adaptive immune systems through different stages of the cancer immunity cycle to produce long-term anti-tumor activity.
Our Myeloid Modulator Platform reawakens myeloid cells to attack tumor cells. We identified monoclonal antibodies that are capable of binding to and agonizing a novel cell surface protein (referred to as Dectin-2*) on tumor-supportive macrophages. The activation of these macrophages results in the production of pro-inflammatory cytokines, consistent with the characteristics of tumor-destructive macrophages. Dectin-2 may have the potential to reprogram tumor-supportive macrophages into tumor-destructive macrophages to elicit a productive anti-tumor immune response. Additionally, KRAS and TP53 mutations may upregulate Dectin-2 on tumor-associated myeloid cells and could provide an avenue to develop precision medicine with an immune modulator.
*Dectin-2, also known as TAM1
