On September 27, 2017 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the first patient has been dosed in the Phase 1 clinical trial (see www.clinicaltrials.gov, identifier NCT03189030) designed to evaluate the safety and tolerability of a personalized live, attenuated double-deleted Listeria monocytogenes (pLADD) immunotherapy for adults with metastatic colorectal cancer that is microsatellite stable (MSS) (Press release, Aduro Biotech, SEP 27, 2017, View Source [SID1234520656]). The personalized immunotherapy has been engineered with patient-specific neoantigens that were identified and selected using state-of-the-art neoantigen identification technology developed by Hanlee Ji, M.D., associate professor of medicine at the Stanford University School of Medicine.
“Our pLADD program leverages our extensive capabilities relating to the use of Listeria as a delivery mechanism for cancer antigens and Dr. Ji’s innovative neoantigen technology used to identify immunogenic antigens specific for an individual patient,” said Natalie Sacks, M.D., chief medical officer of Aduro Biotech. “Together, we believe these two cutting edge technologies represent a new approach to treating patients who have relapsed following prior chemotherapy. We look forward to evaluating initial proof-of-concept in this Phase 1 clinical trial.”
Clinical Design of Phase 1 PLADD Trial in Adults with Metastatic Corlorectal Cancer
The Phase 1 clincial single-arm trial is designed to evaluate the safety and tolerability of a personalized immunotherapy made using patient-specific antigens and Aduro’s proprietary live, attenuated, double-deleted Listeria monocytogenes platform technology. The trial is seeking to enroll approximately 10 patients with metastatic colorectal cancer that is MSS. Patients will receive their patient-specific immunotherapy once every three weeks.
About pLADD
Personalized LADD, or pLADD, is a second-generation LADD technology that is designed to leverage the immune-activating activity of the Listeria bacterial vector in combination with neoantigens, which are unique, patient-specific tumor markers exclusively expressed in an individual’s tumor cells. Once administered, pLADD therapies are expected to mobilize the immune system in two ways–first, through the immediate recognition of the presence of Listeria as being foreign, and subsequently, through a specific and customized immune attack on cells containing the tumor neoantigens presented by pLADD.
To create a patient-specific pLADD therapy, a physician begins by removing tumor cells from the patient. These cells are analyzed in order to molecularly characterize (sequence) the tumor, including any mutations that are unique to the patient’s own tumor cells. Predictive algorithms for antigen processing are run to identify pertinent tumor antigens. Aduro then creates a LADD strain engineered to enable the presentation of multiple selected neoantigens in dendritic cells, with the aim of inducing a targeted, robust anti-cancer immune response.
Preclinical Data with pLADD
Preclinical data showed that mouse pLADD strains targeting tumor-specific neoepitopes induced a robust immune response, including induction of cytokines, chemokines, and antigen-specific CD8+ T cells. In preclinical models of pLADD, remodeling of the tumor microenvironment with an increase in the CD8:Treg ratio was observed. The combination of pLADD with an anti PD-1 agent led to a sustained immune response and significantly improved efficacy in these mouse tumor models.