Source: PACT Pharma
From: PR Newswire
– PACT’s gene-edited T cells were observed to kill tumor cells by targeting patient-specific tumor mutation targets in non-clinical testing
– The company is launching clinical studies of personalized targeted immune cell therapy for patients with solid cancers
PACT Pharma, a leader in the fields of cancer immunology and cell therapy in collaboration with a team at UCLA, presented new data demonstrating for the first time the ability to identify mutation targets unique to each person’s cancer and verify the cancer specificity of multiple cloned T cell receptors. Each patient’s cancer has a private signature of mutations, creating an opportunity to develop fully personalized immune therapies that have the potential to eradicate tumor cells. Defining these cancer mutation targets for each person, known as neoantigens, enables the company to use its proprietary gene engineering technologies to manufacture an immune cell therapy product for each person with cancer. The presentation was at the AACR’s Special Conference on Immune Cell Therapies for Cancer. The company has begun enrolling patients with advanced solid tumors in its Phase 1 dose escalation study of NeoTCR-P1, an autologous gene-edited TCR T cell product that targets personalized neoantigens (https://clinicaltrials.gov/
“These exciting results open a bold new frontier for directing a person’s own immune system to treat patients with solid cancers, an area that hasn’t yet seen the successes of immune cell therapies that we have seen for blood cancers,” said PACT’s Chief Executive Officer Alex Franzusoff, Ph.D. “While it is early, the results demonstrate the possibility for PACT’s approach to ignite a patient’s immune response directly against their unique tumor mutation signature, within a clinically relevant timeframe, with potential applicability to most cancers and all ethnicities across the globe.”
Today’s data is relevant because they show that mutations that build up in tumors, creating the unique tumor mutation “signature” that drives each patient’s cancer, have already triggered each person’s immune system to target those unique mutations, but at a very low level. Now those low-level targeted immune responses can be analyzed with greater accuracy, used to manufacture a truly personalized treatment that is tailored for each patient with cancer, and evaluated in clinical trials.
The company’s approach is designed to select and confirm tumor-exclusive mutations to empower a patient’s immune system to target their specific cancer. PACT utilizes bioinformatics to identify the mutation blueprint of each person’s tumor, and then uses its barcoded snare technologies to capture pre-existing T cells from the blood that already recognize and target the unique mutations. From that group, a proprietary selection platform is used to identify the ideal T cell receptors for specific mutations. Once the target is authenticated, the company uses non-viral gene editing to engineer the ideal mutation-targeted T cell receptors into T cells from the same patient. When reinfused back to the patient, these T cells have the potential to eliminate tumor cells that express these unique mutations.
“The results presented today show that PACT’s approach of neoantigen-specific T cell capture and non-viral precision genome engineering is indeed groundbreaking and promising for a new chapter in personalized immune cell therapies for patients with solid cancers,” said Antoni Ribas, a professor of medicine at the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, who is a co-author of the study and also a co-founder of PACT. “The demonstration that T cell receptor-engineered T cells using the PACT approach can specifically kill that same person’s cancer cells is based on the analysis of immune cells captured from the blood of a patient with a long-lasting response to anti-PD-1 therapy.”
The evolution of personalized immune-oncology treatments
Recently, a new generation of personalized cellular therapies for cancer has emerged. Rapid sequencing technologies, bioinformatics, and genetic/cellular engineering — in addition to a deeper understanding of clinical immunology and a renaissance in immunotherapy — have made these advancements possible. Designer immune-oncology treatments have been developed, including CAR-T cell therapies, cancer vaccines and tumor-infiltrating lymphocyte therapies.
While transformative, these therapeutic approaches face limitations. CAR-T cells only recognize shared cancer targets expressed on the cell surface, which, while effective for blood cancers, have not been applied successfully to patients with solid cancers, and cancer vaccines are often too slow to address a rapidly growing tumor burden. Further, tumor-infiltrating lymphocytes can be impractical—and at times even impossible—to generate for every patient due to the difficulty of isolating limited numbers of specific tumor-targeting immune cells and then needing to greatly expand their numbers for patient dosing. In the case of expanded immune cells in particular, they often become exhausted before reinfusion, which may limit their value for eliminating the cancer throughout the body.
In order to truly tailor cancer treatments to individuals, the therapy must target each patient’s unique cancer signature–including different tissue compatibility receptors of the immune system, or HLA, in each person. These HLA receptors are key to immune recognition, which is what limits organ sharing between people. PACT’s approach captures this nuance. Custom tailored, yet for a global population, PACT’s approach is designed to select and authenticate tumor-exclusive mutations to empower the patient’s immune system to target their specific cancer for a lasting effect. PACT plans to further investigate the safety and effectiveness of this technology in a series of clinical trials, starting with a first-in-human Phase 1 clinical trial at clinical sites in California.
ABOUT PACT –
PACT Pharma is an independent, privately funded company, based in South San Francisco, California, developing transformational personalized TCR-T cell therapies for the eradication of solid tumors and is now enrolling patients in its first-in-human Phase 1 clinical studies at several key academic centers of the CIRM-funded Alpha Clinic network, in California.
PACT Pharma’s accomplished co-founders, David Baltimore (Nobel Laureate), Antoni Ribas, Jim Heath, Terry Rosen and Juan Jaen, established the company in 2016 and launched the company in early 2017. The PACT team raised $31 million in 2016 and secured another $95 million in financing in May of 2018 from Alphabet Inc.’s venture arm GV Investments, Canaan Partners, Casdin Capital, Droia, Foresite Capital, Invus, Pontifax and Wu Capital, including investment from AbbVie Ventures and Taiho Ventures.
PACT Pharma’s technology is designed to reprogram a patient’s immune system cells to target their own cancer. The process involves taking a biopsy of a person’s cancer tissue, sequencing the tumor’s DNA and then using predictive algorithms and proprietary technologies to engineer T-cells involved in the body’s immune response to combat that specific disease as it expresses itself in the patient. The last step is injecting the cocktail back into the patient.
Tumor mutation targeting is programmed into the patient’s own T cells to seek out and kill the tumors. Using (non-viral) precision genome engineering, the mutation-targeted T cell receptors (neoTCRs) are designed to replace the pre-existing T cell receptors of fresh CD8 and CD4 T-cells collected from that same patient followed by minimal expansion in closed systems for re-infusion into the patient. These patient-specific neoTCR-P1 cells are formulated to immediately kill neoantigen-expressing tumors, together with a deep reservoir of ‘ready-to-go‘ neoTCR-P1 cells for long term persistence and which may be capable of rapid expansion to prevent future cancer recurrence.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.