Personalized Gene-Edited Immune Cell Therapy for Patients with Solid Cancers: Verifying Patient-Specific Cancer Mutation Targets

Jul 22, 2019 | Cancer, Cell Therapy, Gene Therapy, Neo-epitopes, Personalized Therapy, Precision Medicine, T Cell Therapy

Personalized Gene-Edited Immune Cell Therapy for Patients with Solid Cancers Verifying Patient-Specific Cancer Mutation Targets

Background: Precision Cancer Therapies

PACT Pharma, a leader in the fields of cancer immunology and cell therapy in collaboration with a UCLA team, presented new data demonstrating for the first time the ability to identify mutation targets unique to each patient’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 caner mutation targets for each patient, known as neoantigens, enables the company to use its proprietary gene engineering technologies to manufacture an immune cell therapy product for each patient with cancer. The company recently presented this ability at the AACR’s Special Conference on Immune Cell Therapies for Cancer.

Phase I Study

The company has begun enrolling patients with advanced solid tumors into a Phase 1 dose escalation study of NetoTCR-P1, an autologous gene-edited TCR T cell product that targets personalized neoantigens. The study is the first-in-human, single-arm, open-label Phase 1a/1b study to determine the safety, feasibility, and efficacy of a single dose of NeoTCR-P1 T cells in patients with solid tumors.

Advance: A Patient’s Own Immune System to Fight Solid Cancers

The latest results presented by sponsor PACT Pharma indicate advancement in directing a patient’s immune system to treat patients with solid cancers. As declared by PACT Pharma CEO Alex Franzusoff, PhD, the goal is to “ignite a patient’s immune response directly against their unique tumor mutation signature, within a clinically relevant timeframe” and in a way that could be applicable to a majority of cancers and ethnicities of patients.

Clinical Investigator Site UCLA Chimes In

Antoni Ribas, professor of medicine at the Jonsson Comprehensive Cancer Center, University of California Los Angeles, and study co-author as well as PACT co-founder reports, “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.”

Professor Ribas continued, “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 the immune cells captured from the blood of a patients with a long-lasting response to anti-PD-1 therapy.”

PACT Pharma Novel Technology

PACT’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 of the 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 Evolution of Personalized Immune-Oncology Treatments

Recently, a new generation of personalized cellular therapies for cancer has emerged. Rapid sequencing technologies, bioinformatics, and gene/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.

These new approaches have faced limitations. To overcome such limitations, researchers must truly tailor cancer treatments to individuals, meaning the therapy must target each patient’s unique cancer signature—including different tissue compatibility receptors of the immune system, or HLA, in each person. PACT’s proprietary 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.

Research Sites

This Phase I first-in-human study will include California clinical investigator sites including:

University of California, Los Angeles, City of Hope, University of California, Irvine, University of California, Davis and University of California, San Diego.

PACT Pharma

Founded in 2016 and based in the biotech cluster of South San Francisco, CA, they are dedicated to synthesizing a tsunami of neo-epitope targeted T cells and producing a personalized adoptive cell therapy designed to benefit each individual cancer patient. The neo-epitope targeting is engineered into the patient’s own T cells (autologous T cells) for programming to seek out, infiltrate into the tumor and kill the tumor cells displaying the unique neo-epitopes. In essence, PACT Pharma is engineering next generation synthetic tumor-infiltrating lymphocytes (synthetic TILs), tailored for each patient’s cancer with highly efficient turnaround in manufacturing from tumor biopsy to re-infusion of autologous synthetic TIL back into the patient.

They have raised $125 million in just a few years since inception.  Anthony Ribas, of UCLA is a founder. Approximately 70 employees report on social network LinkedIn as PACT Pharma employees.


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