- pLADD induced neoantigen-specific CD8+ T cells undetectable before pLADD treatment started
- pLADD induced an innate response exemplified by gamma delta T cells, also thought to be important for successful immunotherapy
Aduro Biotech, Inc. (Nasdaq:ADRO) On 4/26/18 presented preliminary observations from a case study of a patient with metastatic colorectal cancer treated in Aduro’s ongoing Phase 1 study of its personalized neoantigen-based immunotherapy (pLADD). This Phase 1 proof-of-concept study is designed to evaluate the safety and tolerability of pLADD immunotherapy in adults with metastatic colorectal cancer that is microsatellite stable (MSS).
The immunological data presented demonstrated that neoantigens isolated and sequenced from the patient’s tissue samples, and engineered into a personalized immunotherapy, induced neoantigen-specific CD8+ T cells undetectable before pLADD treatment started. In addition to adaptive immunity, pLADD induced an innate response exemplified by gamma delta T cells, also thought to be important for successful immunotherapy. The patient’s neoantigens were selected using state-of-the-art algorithm identification technology developed by Aduro’s collaborator, Hanlee Ji, M.D., associate professor of medicine at the Stanford University School of Medicine.
“Although early, the immunological data obtained from this case study is encouraging, as it indicates that our pLADD immunotherapy has the potential to induce a sustained, antigen-specific effect on the immune system,” said Andrea van Elsas, Ph.D., chief scientific officer of Aduro. “We believe our pLADD approach could offer a differentiated treatment option to patients with MSS colorectal cancer, who represent the vast majority of the colorectal cancer patient population and who have not been responsive to immune checkpoint inhibitors. In addition, these preliminary observations support our plan to combine pLADD with checkpoint inhibitors, which we believe could enhance the overall response in this patient setting. We look forward to reporting additional immunological data from this Phase 1 trial before the end of 2018.”
Personalized LADD (personalized live, attenuated, double-deleted Listeria monocytogenes), 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 pLADD 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.
Aduro received an exclusive license (for use with Listeria based therapetutics) to the proprietary bioinformatics algorithms and computational workflows for neoantigen identification and selection from Stanford University based on technology developed by Dr. Hanlee Ji. The accurate identification of neoantigens, tumor markers that are unique to an individual’s tumor, is believed to be critical in the development of a patient-specific cancer treatment. Aduro’s LADD technology, which has been shown in clinical studies to remodel the tumor microenvironment, will be used to create a patient-specific immunotherapy that is engineered to enable the presentation of multiple selected neoantigens in dendritic cells, with the aim of inducing a targeted, robust anti-cancer immune response.