Probiotic-guided CAR-T cell system for targeted cancer immunotherapy

This technology is an engineered probiotic bacteria-guided CAR-T immunotherapy system for the treatment of various types of cancer, including solid tumors.

Unmet Need: Effective immunotherapy for solid tumors

Immunotherapy is FDA approved for the treatment of an increasing number of cancers; however, the overall patient response rate for immunotherapy remains low. This is due to the hypoxic and immunosuppressive tumor microenvironment, which does not allow for immune cells to infiltrate the tumor. Solid tumors have an especially low immunotherapy response rate, hindering the use of immunotherapy in patients with certain types of cancer.

The Technology: Probiotic-guided CAR-T system for enhanced cancer immunotherapy

This technology employs an engineered probiotic bacteria-guided CAR-T system for cancer treatment. The engineered bacteria colonize tumors and release synthetic proteins, which the CAR-T cells are programmed to recognize and respond to. The bacteria can also release chemokines to attract immune cells to the tumor sites and activate an immune response against the tumor.

This technology has been validated in xenograft models of human lymphoma and solid tumor models.

Applications:

• Immunotherapy for cancer treatment, inflammatory diseases, and autoimmune diseases
• Immunotherapy for treatment of other hyperproliferative disorders
• Research model for studying immunotherapy

Advantages:

• Improved efficacy of immunotherapy
• Low toxicity/off target effects
• No proven resistance
• Targets and modulates immunosuppressive tumor microenvironments
• Expands to different types of cancer including solid tumors
• More targeted than standard immunotherapy

Lead Inventor:

Tal Danino, Ph.D.

Patent Information:

Patent Pending (US/2024/0016847)

Related Publications:

• Savage TM, Vincent RL, Rae SS, Huang LH, Ahn A, Pu K, Li F, de los Santos-Alexis K, Coker C, Danino T, Arpaia N. “Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity” Sci Adv. 2023 Mar; 9(10)

• 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)

• Serebrinsky-Duek K, Barra M, Danino T, Garrido D. “Engineered Bacteria for Short-Chain-Fatty-Acid-Repressed Expression of Biotherapeutic Molecules”. Microbiol Spectr. 2023 Mar 20;11(2)

• Doshi A, Shaw M, Tonea R, Moon S, Minyety R, Doshi A, Laine A, Guo J, Danino T. “Engineered bacterial swarm patterns as spatial records of environmental inputs”. Nat Chem Biol. 2023 Jul;19(7)

• 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)

Tech Ventures Reference:

• IR CU21194, CU22211

• Licensing Contact: Cynthia Lang