Technology

Targeted Granzyme B Immunotherapy (TGI)

Our ADC platform harnesses the precision of antibodies to deliver granzyme-based cytotoxic agents directly to tumor cells, sparing healthy tissues and reducing side effects.

Targeted Granzyme B Immunotherapy (TGI) Platform

At AbBC Therapies, we are pioneering a next-generation Targeted Granzyme B Immunotherapy (TGI) platform that merges the tumor-targeting precision of antibody–drug conjugates (ADCs) with the potent, natural killing mechanism of immune effector proteins—into a single, fully biologic hybrid molecule.
This innovative construct is designed to deliver highly selective, durable tumor killing while minimizing systemic toxicity and simplifying manufacturing.

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Mechanism and Molecular Design

Novel, Patented Antibody–Granzyme B Configuration

  • A fully human, catalytically active Granzyme B (GrB) protein is fused to a human synthetic antibody or antibody fragment that recognizes a tumor-specific antigen.
  • The resulting fusion molecule is circulating-stable and non-toxic in systemic circulation.
  • GrB’s prolonged serum half-life (~35 hours) enables enhanced tumor accumulation and sustained exposure at the disease site.
  • Upon antigen-mediated endocytosis, the conjugate is internalized and delivers GrB directly into the cytosol of the cancer cell, where it triggers apoptosis.
  • The modular architecture allows universal pairing of GrB with virtually any antibody or targeting ligand, providing broad adaptability across indications.

Targeted Granzyme B Platform: A Class Beyond Cytotoxic Agents

AbBC’s TGI platform introduces a fundamentally new therapeutic class—biologic Granzyme B conjugates that retain the precision of ADCs but replace chemical payloads with a natural cytotoxic enzyme.

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Key advantages

Novel, Patented Antibody–Granzyme B Configuration

  • Fully human composition — no synthetic toxins or chemical linkers.
  • Mechanism of action mirrors T-cell cytotoxicity (as in CAR-T therapy) yet bypasses immune checkpoints, enabling broader and more consistent tumor killing.
  • IgG dimerization (~160 kDa) extends half-life and optimizes pharmacokinetics.
  • Internalized GrB remains catalytically active in both released and retained forms, ensuring sustained intracellular activity.
  • Unconjugated GrB is biologically inert to normal cells, reinforcing its favorable safety profile.
  • Manufacturing simplicity — the GrB–antibody conjugate is produced through a standard antibody manufacturing process, without the complexities of chemical conjugation.
  • Demonstrated preclinical safety and efficacy:  - Example: GrB–Antibody shows a maximum tolerated dose (MTD) > 500 mg/kg in mice, with a wide therapeutic index and efficacy at 40–150 mg/kg.

Mode of Action: Targeted Delivery of Granzyme B

  • Target Recognition — The antibody fragment selectively binds to tumor-associated antigens.
  • Internalization — The GrB conjugate is internalized through receptor-mediated endocytosis.
  • Cytosolic Release — Granzyme B enters the cytosol of the cancer cell.
  • Cell Death Activation — GrB triggers apoptosis through caspase cleavage, mitochondrial disruption, and DNA fragmentation, while also promoting immunogenic cell death that recruits and activates the immune system.
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The AbBC TGI platform unites antibody precision, immune killing power, and biologic manufacturability into one therapeutic entity—establishing a new class of safer, scalable, and more effective targeted therapies for oncology and ophthalmology.