This technology is an engineered bacteria capable of directing immunomodulatory therapeutics, such as recombinant nanobodies, cytokines, and tumor neoantigens, into targeted tumors.
Unmet Need: Targeted delivery approaches for cancer immunotherapies
Chemotherapies and other classical systemic cancer therapies are plagued by deadly side effects due to no specificity and toxicity. The ability to target such therapies directly to the tumor would not only reduce the severity of side effects but would also improve the efficacy of the therapy.
The Technology: Programmable bacteria for tumor-targeted immunotherapy
This technology is an engineered bacteria that specifically targets tumors to release targeted therapeutics, including recombinant nanobodies, cytokines, and tumor neoantigens. This technology makes it possible to flood the local tumor microenvironment with higher concentrations of pharmacological agents, thereby improving the efficacy of the drug while reducing unintended side effects.
This technology has been validated in a mouse model of lymphoma.
Applications:
- Treatment for solid tumors such as lymphomas
- Synergistic combination therapy with existing chemotherapeutics
- Labeled bacteria strain for identifying and targeting tumors in the body
Advantages:
- Reduces risk of systemic side effects from immunotherapies
- Increases efficacy of treatment by increasing local concentration of pharmacological compounds
- Can be readily modified to target other types of diseases
Lead Inventor:
Tal Danino, Ph.D.
Patent Information:
Patent Pending (US20210308195)
Related Publications:
Vincent RL, Gurbatri CR, Li F, Vardoshvili A, Coker C, Im J, Ballister ER, Rouanne M, Savage T, de Los Santos-Alexis K, Redenti A, Brockmann L, Komaranchath M, Arpaia N, Danino T. “Probiotic-guided CAR-T cells for solid tumor targeting.” Science, 2023 Oct 13; 382(6667): 211-218.
Gurbatri CR, Radford GA, Vrbanac L, Im J, Thomas EM, Coker C, Taylor SR, Jang Y, Sivan A, Rhee K, Saleh AA, Chien T, Zandkarimi F, Lia I, Lannagan TRM, Wang T, Wright JA, Kobayashi H, Ng JQ, Lawrence M, Sammour T, Thomas M, Lewis M, Papanicolas L, Perry J, Fitzsimmons T, Kaazan P, Lim A, Stavropoulos AM, Gouskos DA, Marker J, Ostroff C, Rogers G, Arpaia N, Worthley DL, Woods SL, Danino T. “Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.” Nat Commun. 2024 Jan 20; 15(1): 646.
Redenti A, Im J, Redenti B, Li F, Rouanne M, Sheng Z, Sun W, Gurbatri CR, Huang S, Komaranchath M, Jang Y, Hahn J, Ballister ER, Vincent RL, Vardoshivilli A, Danino T, Arpaia N. “Probiotic neoantigen delivery vectors for precision cancer immunotherapy.” Nature. 2024 Nov; 635(8038): 453-461.
Li F, Yang Z, Savage TM, Vincent RL, de Los Santos-Alexis K, Ahn A, Rouanne M, Mariuzza DL, Danino T, Arpaia N. “Programmable bacteria synergize with PD-1 blockade to overcome cancer cell-intrinsic immune resistance mechanisms.” Sci Immunol. 2024 Oct 18; 9(100): eadn9879.
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