Chinese Scientists Develop STAR-T Cell Therapy More Effective Than CAR-T Against Solid Tumors, Files IPO Prospectus

May 5, 2021 /BioValleyBIOON/---Current chimeric antigen receptor (CAR) T-cell (CAR-T) therapies are primarily used to target blood cancers. T cells are isolated from the patient’s blood and genetically engineered in the laboratory to express CARs. These specially modified T cells (CAR-T cells) are then expanded extensively in vitro. The CAR receptors expressed on their surface are critical, as they bind to a specific protein on the surface of the patient’s cancer cells, thereby destroying the cancer.

Once equipped with chimeric antigen receptors (CARs), CAR-T cells are reinfused into the patient, where they become powerful combat units numbering in the millions. Some physicians refer to these specially armed T cells as “living drugs” because they can fight cancer around the clock. Others consider CAR-T cell therapy to be a convergence of cellular therapy, gene therapy, and immunotherapy.

Regardless of how this therapy is defined, CAR-T cell therapy has become a treatment for B-cell lymphoma and certain forms ofLeukemiaa breakthrough form. Pediatric patients have consistently been among the greatest beneficiaries, as this therapy has demonstrated particular efficacy in younger populations compared to adults. Two CAR-T cell products have already been approved by the U.S. Food and Drug Administration (FDA) approved for market launch. Kymriah (tisagenlecleucel) isNovartisOne of the company’s CAR-T cell products was approved for market launch in August 2017, followed by Yescarta (axicabtagene ciloleucel), which received approval in October of the same year. Yescarta was developed by Kite Pharmaceuticals, based in California.

However, both in pediatric and adult patients, solid tumors have cleverly evaded the ability of CAR-T cell therapy to halt cancer. Malignancies of the brain, breast, colon, lung, and prostate are inaccessible to these CAR-T cells. Scientists state that for these types of cancers, CAR-T cells do not persist long enough to achieve tumor destruction.TumorCells.

In a new study, researchers from Tsinghua University, the Tsinghua-Peking University Joint Center for Life Sciences, Capital Medical University, and Huaxia Yingtai (Beijing) Biotechnology Co., Ltd.Researchers have collaboratively developed a synthetic T-cell receptor for anticancer therapy that enhances T-cell potency through distinct mechanisms, showing promise in combating solid tumors. By addressing two prominent limitations of CAR-T therapy, this synthetic T-cell receptor not only possesses the ability to seek out and destroy solid tumors while sparing healthy tissues, but also confers robust persistence upon this anticancer weapon to ensure task completion.The relevant research findings were recently published in the journal Science Translational Medicine, under the title “Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors”.

Although conducted solely in animal models, this new study represents a promising step toward novel CAR-T cell therapies for solid tumors, one of the hottest topics in the global race in recent years.This novel approach, termed STAR-T cell therapy, differs from CAR-T cell therapy in its development methodology (utilizing synthetic receptors) and its mechanism of leveraging potent cell signaling activity to target cancer antigens. Like CAR-T cells, STAR-T cells, upon activation, pursueTumorcells and kill cancer.

These authors wrote that CAR-T cell therapy has been used in the treatment of B-cell malignanciesTumoraspects, demonstrating high response rates and durable disease control; however, in solid tumors, CAR-T cells exhibit limited efficacy, which is partly attributed to intrinsic defects in CAR signaling transduction.

In various mouse models, STAR-T cells demonstrated superior control over multiple solid tumor types compared to CAR-T cells. In these experiments, STAR-T cells did not undergo functional exhaustion, as is commonly observed with CAR-T cells in the treatment of solid tumors.These authors point out that the functional exhaustion and inefficacy of CAR-T cells are due to a phenomenon known as antigen-independent signaling (tonic signaling), which is characterized by the persistent activation of dysregulated T cell signaling. Additional challenges exist when CAR-T cells are used for the treatment of solid tumors: they are susceptible toTumorinhibited by internal and surrounding molecules.

In this new study, STAR-T cells rapidly induce in patients with glioblastoma andLiver CancerTumor regression was observed in test mice with lung cancer, demonstrating potent activity against solid tumor cells. None of these mice showed evidence of side effects. STAR mediates robust and sensitive T-cell receptor-like signal transduction; STAR-T cells exhibit less dysfunction and better proliferation than conventional CAR-T cells. Furthermore, STAR-T cells display higher antigen sensitivity than CAR-T cells, which holds clinical potential for reducing antigen loss and inducingTumorThe potential for recurrence risk.

While these authors focused on solid tumors in mouse models as the target of their STAR-T cell research, a research team from the Lu Daopei Institute of Hematology in Beijing was conducting a Phase I clinical trial involving STAR-T cell therapy in humans.Clinical Trial, to determine the tolerance of people to STAR-T cells.

This clinical study did not analyze the efficacy of STAR-T cell therapy for solid tumors, but evaluated STAR-T cell infusion for the treatment of relapsed B-cell acute lymphoblastic leukemia. Dr. Lu Daopei and his team stated that thisClinical Trial"It is a first-in-human study aimed at determining the technical feasibility, clinical safety, and efficacy of STAR-T cells, which have the potential to better identify and target than traditional CAR-T cells."Tumorintracellular antigens. Furthermore, STAR-T cells are easier to construct, offering great promise for the treatment of solid tumors. (Bioon.com)

References:

Yue Liu et al. Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors. Science Translational Medicine, 2021, doi:10.1126/scitranslmed.abb5191.