ImmunoCellular's Stem-to-T-Cell program is designed to provide a novel method of harnessing a patient’s immune system to manufacture antigen-specific killer T cells that target and destroy cancer cells and provide long-term immuno-surveillance against tumor recurrence. The Stem-to-T-Cell platform has the potential to address many types of cancer, including both solid and hematological tumors.
Immunotherapies are being widely investigated as a way to develop highly specific anticancer therapies. The goal of most of these immunotherapies is to create a population of killer T cells that are programmed to destroy tumor cells.
ImmunoCellular’s Stem-to-T-Cell platform represents a novel and more direct approach to generating killer T cells by using the patient’s stem cells as starting material. The Stem-to-T-Cell technology thus shares some similarities with other immuno-oncology technologies, such as CAR-T, and could potentially be used in combination approaches. Unlike CAR-T therapies which deliver a large bolus of active T cells into the patient’s circulation and have been associated with toxicity in some patients, ImmunoCellular’s approach enables a more gradual and measured release of killer T cells and has the potential for lower toxicity while also yielding a more sustained response.
ImmunoCellular has been working diligently on advancing and achieving the milestones for this program. In March 2017, the company announced the successful sequencing of a target T cell receptor gene, which was a key step in advancing toward identification of a potential clinical candidate. The sequenced T cell receptor, or TCR, will be utilized in a proof-of-concept evaluation for the Stem-to-T-cell program.
The isolation of selected T cells and identification of the genetic sequence of their receptor was performed in the laboratory of Dr. Cassian Yee at the University of Texas MD Anderson Cancer Center. In November 2015, ImmunoCellular entered into a sponsored research agreement with MD Anderson, with Dr. Cassian Yee as principal investigator, which focused on identifying T cells that find and kill tumor cells expressing a target antigen. The ultimate goal of this work is to establish a clinical program based on hematopoietic stem cells that are isolated from the patient, then modified with the TCR gene sequence, and returned to the patient. These modified stem cells would self-replicate and also continually produce antigen-specific killer T cells that target and kill the tumor.
The critical starting point for this novel therapeutic strategy was to isolate and identify T cells that can selectively attack and destroy target tumor cells. The genetic sequence of the unique receptor on that population of T cells is what is transferred into hematopoietic or blood stem cells. When inserted into a blood stem cell, expression of this TCR gene is expected to drive the patient’s immune system to produce killer T cells programmed to attack tumors. This Stem-to-T-Cell therapeutic strategy has the potential to provide a safer, sustainable and more specific immune treatment for cancer. Achieving this milestone required completion of several critical steps: the collection and analysis of multiple clones of cells containing the target TCR genes, harvesting the plasmids with the TCR gene, and then sequencing that gene.
ImmunoCellular is now engaged in the next phase of this research, which is to focus on packaging the T cell receptor sequence into a lentivirus vector. This packaged lentivirus is the vehicle that will be used to transfect human hematopoietic stem cells. The transfected stem cells will then be monitored for any phenotypic changes. These hematopoietic stem cells could become, in essence, an internal factory producing antigen-specific killer T cells in the patient. Once these fundamental elements are in place, a product candidate for testing in cell lines and suitable preclinical models may be generated. Successful testing would potentially lead to human clinical trials.
Key anticipated 2017-2018 milestones in this program include: completion of loading of the T cell receptor DNA sequence into a viral vector and transfection of the human hematopoietic stem cells by the loaded viral vector. These transfected stem cells are anticipated to ultimately be able to produce an unlimited supply of killer T cells bearing the desired T cell receptor. The killer T cells are designed to specifically target and destroy tumor cells. This phase of the Stem-to-T-Cell program is an important component of the proof-of-concept work for this technology. Once proof-of-concept has been established, the company can progress to testing in preclinical models.
ImmunoCellular’s collaboration with the University of Maryland, established in January 2016, is also moving forward. This collaboration is focused on gaining a better understanding of strategies to improve immunotherapies.