Our Science

Our Boltbody™ platform consists of systemically delivered Immune-Stimulating Antibody Conjugates (ISAC). We conjugate tumor-targeting antibodies to powerful immune stimulants such as TLR agonists, proven to convert cold tumors into immunologically hot tumors, and have demonstrated that Boltbody™ ISACs eliminate tumors in preclinical models following systemic administration.

Addressing Cancer Systemically

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IMMUNE TARGETED THERAPY

Checkpoint inhibitors, such as anti-PDL1, take the brakes off patient’s T cells so they can kill tumor cells. Checkpoint inhibitor therapy has proven to extend patient survival, but is not effective for many because the patient’s tumor is immunosuppressive (“cold”). To address this issue, clinical trials demonstrate that therapies targeting Toll-Like Receptors (TLR) in the tumor can re-activate the immune system, often enabling tumor shrinkage in combination with checkpoint therapy. However, TLR therapy generally requires intratumoral injection because systemic delivery can promote non-specific immune activation, leading to safety or tolerability issues.

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TUMOR TARGETED THERAPY

Systemic administration of tumor-targeting agents enables cancer treatments to reach tumors inaccessible by direct intratumoral injection and to reach metastatic disease. Specifically, monoclonal antibodies (mAb) can be administered systemically and are targeted to the site of disease where tumors express the target antigen. MAb therapies are augmented by Antibody Drug Conjugates (ADC) where chemotherapeutic drugs are chemically linked to mAbs. This permits highly-toxic payloads to selectively eliminate targeted tumor cells while sparing healthy tissue.

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TUMOR & IMMUNE TARGETED THERAPY

Immune Stimulating Antibody Conjugates (ISAC) link powerful immune-stimulating payloads, such as TLR agonists, to tumor targeting mAbs and are systemically delivered.  This novel therapeutic has demonstrated tumor eradication as a monotherapy in preclinical models and activation of the innate immune system to generate an adaptive immune response which leads to durable T cell-mediated tumor clearance and surveillance. Bolt’s considerable experience in dendritic cell biology and insight into the human immune system led to the discovery of the Boltbody™️ ISAC.

The Boltbody™ platform reinvigorates the immune system and builds on our understanding of how dendritic and other myeloid cells generate effective anti-tumor immunity. Boltbody™ ISACs are a unique class of immuno-oncology therapies whose capabilities hold the promise of generating systemic immunological memory with durable clinical benefit.

Dr. Edgar G. Engleman, M.D., Director, Immunology & Immunotherapy of Cancer Programs, Stanford Cancer Institute. Bolt Founder and Board Member.

THE PROMISE OF IMMUNOLOGICAL MEMORY

Boltbody™ ISACs selectively target tumors for destruction by the immune system. Tumor-associated myeloid cells engulf ISAC-bound tumors, become armed with tumor neoantigens, and migrate to the lymph nodes where they mediate the activation and expansion of tumor-reactive T cells. In preclinical tumor models, ISAC therapy leads to regression of established tumors and generation of immunological memory, which guards against the recurrence of tumors that express tumor neoantigens even if they no longer express the ISAC target antigen.

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Bolt Biotherapeutics is a vibrant biotechnology company actively developing its novel Boltbody™ platform, a cancer immunotherapy that consists of Immune-Stimulating Antibody Conjugates (ISAC). Located in the San Francisco Bay Area, Bolt is led by a team with extensive oncology drug development experience and is seeking bright, self-motivated individuals who share their passion for bringing novel and curative biotherapies to patients in need. If you enjoy a collaborative and fun environment with all the benefits and challenges that come with working at a cutting-edge biotherapeutics company, please contact us at 650.665.9295 or jobs@boltbio.com for more information.

Here are some positions we’re hiring:

Scientist/Senior Research Associate, Biomarkers and Translational Science
Associate Director/Director, Head of Bioconjugation
Scientist II/Sr. Scientist - Cell Culture Lead
Senior Director, Human Resources

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Boltbody™ Immune-Stimulating Antibody Conjugates

Bolt Biotherapeutics, Inc.
640 Galveston Drive
Redwood City, CA 94063