We developed a platform for engineering B cells via targeted integration of antibody sequences into the immunoglobulin heavy chain (IgH) locus, enabling physiological expression as a B cell receptor (BCR) and subsequent antigen-induced secretion. Unlike conventional antibody therapies or ectopic expression systems, this approach preserves key adaptive immune functions including antigen-dependent activation, class-switch recombination (CSR), somatic hypermutation (SHM), affinity maturation, and immunological memory. Engineered B cells thus function as a “living and evolving drug,” capable of sustained and adaptive therapeutic responses across infectious diseases, cancer, and autoimmune disorders.

UNMET NEED

• Monoclonal antibody therapies require repeated administration due to limited half-life and high cost
• Risk of anti-drug antibodies and loss of efficacy
• Lack of adaptability to evolving targets (e.g., viral escape, tumor heterogeneity)
• Existing gene therapy approaches (e.g., muscle expression) do not support:
  • affinity maturation
  • class switching
  • immunological memory
• Current cell therapies (e.g., CAR-T) face limitations in persistence, escape, and solid tumors

OUR SOLUTION

• A genome-engineering platform targeting the IgH locus to introduce antibody sequences as functional BCRs, enabling:

• Physiological regulation of antibody expression (membrane + secreted forms)
• Antigen-dependent activation (not constitutive expression)
• Adaptive evolution in vivo, including:

• somatic hypermutation (SHM)
• class-switch recombination (CSR)
• clonal selection and expansion
• memory formation

• Compatibility with both ex vivo and in vivo delivery approaches

This creates a self-renewing, evolving therapeutic modality rather than a static drug.

APPLICATIONS

• Infectious diseases (e.g., HIV broadly neutralizing antibodies)
• Cancer immunotherapy
  • direct antibody-mediated killing
  • antigen presentation and T-cell activation
• Autoimmune diseases (antigen-specific immune modulation)
• Vaccinology / durable immunity platforms
• Potential platform for in vivo programmable immunity

MARKET / POTENTIAL MARKET

• Global monoclonal antibody market: >$200B annually
• Rapidly growing cell and gene therapy market
• Oncology immunotherapy market (including CAR-T): >$100B projected
• Infectious disease biologics (HIV, RSV, etc.)
• Potential to replace chronic biologic dosing with single-shot therapies

STATUS

• Robust preclinical proof-of-concept demonstrated:
  • engineered B cells produce high antibody titers
  • undergo CSR, SHM, and clonal selection
  • show memory retention and boost responsiveness
• Demonstrated in vivo engineering via AAV delivery
• Expansion into oncology applications (HPV, tumor antigens)
• Platform being advanced translationally (Tabby Therapeutics)

INTELLECTUAL PROPERTY

• WO2020/053865 GENETIC ENGINEERING OF B CELL RECEPTORS AND USES THEREOF IN ANTIGEN-INDUCED ANTIBODY SECRETION
• WO 2023/144820 ENGINEERING B CELLS TO EXPRESS CHIMERIC ANTIGEN RECEPTORS (CARS) AND USES THEREOF FOR T CELL INDEPENDENT ACTIVATION

REFERENCES

• Nahmad et al., Nature Communications (2020) – Engineered B cells enable memory, CSR, and clonal expansion
• Nahmad et al., Nature Biotechnology (2022) – In vivo B cell engineering using AAV
• Guberman Bracha et al., Frontiers in Immunology (2025) – B cell engineering for cancer
• Boucher et al., Frontiers in Immunology (2025) – Engineered human B cells demonstrate antigen presentation and antibody-mediated anti-tumor functions