A personalized CAR-T to attack every solid tumor? Pact Pharma has a plan

The American Association for Cancer Research (AACR) held a special conference over the weekend focused on the challenges of using patients’ own immune cells to design personalized therapies against their cancers. Among the biggest questions addressed at the San Francisco gathering was, how can chimeric antigen receptor T-cell (CAR-T) and other immuno-oncology treatments that have greatly improved the prognoses for patients with some blood cancers be expanded to treat solid tumors?

Startup Pact Pharma, working with researchers at the University of California, Los Angeles (UCLA), presented new data on a strategy they hope will provide a solution to that problem. The company's approach entails defining specific cancer mutations in each individual patient and then manufacturing an immune-cell therapy that targets abnormal proteins, or “neoantigens,” produced by genes with those mutations.

The company announced it has launched a phase 1 study of the technique in patients with solid tumors.

The process starts by using bioinformatics technology to identify the “mutation blueprint” of each patient’s tumor, according to a statement. From there, Pact’s scientists can capture T cells in the blood that already have the ability to recognize and target those mutations.

The researchers then identify mutation-targeted T-cell receptors and use gene editing to attach them to T cells from the patients. The resulting product, called NeoTCR-P1, will be infused back into the patients. The company hopes to show in clinical trials that the engineered T cells will eliminate tumors that express the mutations they were designed to target.

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At the AACR gathering, the UCLA researchers presented data from a study in which they used Pact's technology to identify mutations in melanoma samples from two patients: one who responded to a drug that inhibits PD-1, an immune checkpoint, and another who didn’t. Then they made T cells specific to those mutations and showed they could use them to kill melanoma cells from the patients.

"We hope that a better understanding of the T cell responses that occur after immune checkpoint blockade will guide the design of personalized adoptive T cell therapies," said Cristina Puig-Saus, Ph.D., associate project scientist in hematology/oncology at the David Geffen School of Medicine at UCLA, in a statement.

Designing CAR-Ts to target neoantigens is one of several approaches being tried in the fight against solid tumors. Earlier this month, researchers at the Massachusetts Institute of Technology released a study showing they could eliminate solid tumors in mice using a vaccine containing an antigen that stimulates CAR-T cells in lymph nodes. And at the AACR annual conference in March, two separate research groups presented promising early studies on solid-tumor-targeting CAR-T cells, one aimed at HER2-positive sarcomas and the other at malignant pleural disease caused by mesothelioma.

Pact Pharma was co-founded in 2017 by several researchers including Antoni Ribas, a professor of medicine at UCLA’s Jonsson Comprehensive Cancer Center. The company raised $126 million in two funding rounds from investors including Taiho Ventures, AbbVie Ventures and Alphabet's GV.

Pact aims to enroll 148 patients in its phase 1 trial of NeoTCR-P1, which it plans to study both as a solo treatment and as a combination with the anti-PD-1 drug Opdivo. The company’s researchers believe the results presented at the AACR conference “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,” said Alex Franzusoff, Ph.D., CEO of Pact, in the company’s statement.