New immunotherapy moves further into clinical testing with promising results

By Samantha Black, PhD, ScienceBoard editor in chief

August 6, 2019 -- Success in international clinical trials leads to U.S. based research organizations beginning phase I/II clinical trials. If this form of immunotherapy is successful and deemed safe, then it could save the lives of liver cancer patients across the world.

Hepatocellular carcinoma (HCC) is a rare disorder in the United States, but the most common primary tumor of the liver. According to the National Organization for Rare Disorders there are approximately six new cases of HCC per every 100,000 people in the general population of the U.S. The number of people who develop HCC in the U.S. has risen in the last four decades. About 31,780 people will die of liver cancers in 2019.

The ET140202 ARTEMIS AbTCR T-cell receptor platform is a novel proprietary technology that was designed to utilize the natural biology of T-cells to fight cancer potential to eliminate T-cell hyperactivation and consequently, cytokine release syndrome (CRS). The platform contains two domains: an antibody-based antigen-binding domain and an effector domain.

HCC is associated with elevated levels of alpha fetoprotein (AFP). Moreover, HLA-A2 (human leukocyte antigen) is a major histocompatibility complex (MHC) antigen specific to humans. HCC cells express HLA antigens strongly. A clinical trial is now underway for patients who are AFP-positive and HLA-A2 positive. The engineered ET140202 T cells recognize and bind to the AFP peptide/HLA-A2 complex (a small protein/antigen highly expressed in HCC), become activated and kill the liver tumor cells.

According to Eureka Therapeutics the system uses:

“proprietary human TCR-mimic (TCRm) antibody to target an AFP-peptide/HLA-A2 complex on HCC cancer cells. Using its proprietary E-ALPHA® antibody discovery platform, Eureka discovered and developed a TCRm antibody to selectively bind upon fragments or peptides of the AFP protein that are broken down within the cancer cell proteasome and displayed on the cell surface by the major histocompatibility complex (MHC). Once engaged onto this complex, the ET140202 engineered T-cell is designed to be activated to kill the cancer cell.”

City of Hope is the first institution in the United States to open an immunotherapy clinical trial for liver cancer. The clinical trial tests for safety and tolerability of ET140202 T cells. If the initial study participants react favorably, the trial will move into drug efficacy testing. The study aims to assess patients for two years and to follow them for 15 years post-treatment.

Eureka Therapeutics issued a press release on August 5, 2019 stating the preliminary results of their China based clinical trials. ET140202 T cell therapy was first tested in China in a first-in-human, proof-of-concept study. The ongoing study has demonstrated a favorable safety profile in six patients with no CRS (serious side effect that includes overexpression of certain proteins) or drug-related neurotoxicity (side effects). In addition, one patient in the i.v. arm of the study had a complete response. Overall, tumor regression was observed in three out of six patients.

The goal is to create a true targeted approach to using immune cells to home in on only tumors, and nothing else. “The novel T cell platform has the potential to transform T cell therapy into an outpatient procedure,” said Yuman Fong, M.D., director of the Center for Surgical Innovation at City of Hope, co-investigator of the ongoing clinical trial and The Sangiacomo Family Chair in Surgical Oncology. “We, Eureka Therapeutics and others are designing T cell therapies with low toxicity.”

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