On November 9, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that Tom Dubensky Jr., Ph.D., chief scientific officer of Aduro, presented today about the company’s personalized LADD technology at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) distinct session titled New Cancer Immunotherapy Agents in Development being held in conjunction with the SITC (Free SITC Whitepaper) annual meeting (Press release, Aduro BioTech, NOV 9, 2016, View Source;p=RssLanding&cat=news&id=2221061 [SID1234516456]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
LADD is Aduro’s proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to express tumor-associated antigens to induce an innate immune response and tumor-specific T cell-mediated immunity. Personalized LADD, or pLADD, is a second generation LADD technology that is being designed for individualized, patient-specific immunotherapy. The pLADD approach leverages the immune activating activity of the Listeria bacterial vector in combination with neoantigens, or the tumor markers specific to an individual’s cancer, which are derived from the patient’s own unique tumor cells. Once administered, pLADD therapies are expected to mobilize the immune system through first an immediate recognition of the presence of Listeria as being foreign and then second a specific and customized immune attack on cells containing the tumor neoantigens presented by pLADD. An Investigational New Drug (IND) application has been accepted, and a Phase 1 trial evaluating the safety and immunogenicity of pLADD in patients with advanced gastro-intestinal cancers is planned.
"There is tremendous excitement in the oncology field to develop personalized therapies as the next new wave in immunotherapy to specifically customize treatment for each patient based on neoantigens that are unique to a patient’s tumor," said Tom Dubensky Jr., Ph.D., chief scientific officer of Aduro. "We are excited about the potential of our pLADD program, which has been shown to induce anti-tumor immune responses specific to tumor neoantigens and correlate with longer survival in preclinical models. Additionally, in these models, we observed a synergistic anti-tumor effect when pLADD was combined with an anti-PD-1 antibody, resulting in a significant reduction in tumor volume and increased survival."
The pLADD technology platform is well-suited to maximize the potential benefit of personalized therapy through the ability to engineer the therapy with multiple tumor-specific neoantigens, as well as to leverage an efficient small-scale manufacturing process in its production.
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 that includes the patient-specific neoantigens for administration.
Preclinical Data with pLADD
Preclinical data showed that pLADD induced a robust immune response, including broad innate immune responses involving cytokines, chemokines, natural killer, and gamma delta T cells, as well as antigen-specific adaptive T cell responses (CD8+ and CD4+). In preclinical models, pLADD remodeled the tumor microenvironment, whereby an increase in infiltration of neutrophils, T cells and dendritic cells was observed. The combination of pLADD with an anti-PD-1 led to a sustained immune response and significant prolongation of survival in these models.
Detailed preclinical data will be presented by Aduro scientist Meredith Leong, Ph.D., on Saturday, November 12, 2016 at the SITC (Free SITC Whitepaper) Annual Meeting (Poster #366).