Gene & Cell Therapy’s Big Leaps in the Past 5 Years

Gene therapy allows doctors to treat disorders by altering one’s genetic makeup instead of conventional drugs and surgeries. The technology treats diseases by fixing a genetic alteration underlying a disorder, activating a gene to help fight diseases, turning off a malfunctioning gene, and removing a segment of DNA that is impairing normal functions. Currently, gene therapy is utilized to treat cancers, hereditary diseases, and infectious diseases.

CAR-T Drives Collaborations Between Drug Manufacturers and Biotechs

Chimeric antigen receptor T-cells (CAR-T) therapy is a new type of immunotherapies, it is a combination of cell and gene therapy most suitable for cancer treatment. They are made by collecting T cells from the patient and re-engineering them in a laboratory to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells. After the re-engineered T cells are cultured into millions in the labs, they are then re-infused into the patient. These cells will continue to multiply in the patient’s body, recognize and eliminate any cancer cells presenting the target antigen on their surfaces with guidance from their CAR receptors.

In 2017, the FDA approved its first CAR-T therapy for acute lymphoblastic leukemia (ALL) in children. Since then, six CAR-T therapies have been approved by the FDA: Novartis’ Kymriah (tisagenlecleucel), Bristol Myers Squibb’s Abecma (idecabtagene vicleucel), Janssen’s Carvykti (ciltacabtagene autoleucelin), Kite Pharma’s Yescarta (axicabtagene) and Tecartus (brexucabtagene autoleucel), and Juno Therapeutics’ Breyanzi (lisocabtagene maraleucel). Abecma in particular is the first cell-based gene therapy indicated for multiple myeloma.

Related article: Scientists Engineer RNA Switches for Targeted Delivery of Gene Therapy and RNA Therapeutics 

Placental Stem Cells Accounted for Most Cell Therapies

Cellular therapies work by culturing autologous (own) or allogeneic (from donor) cells outside the body, then reintroducing these cells back into the body to achieve therapeutic effects.

The initial development of cell therapy is different from gene therapy, which is mainly used to suppress rejection after organ or bone marrow transplantation; gene therapy focuses on rare diseases or genetic diseases. However, both treatments are classified as advanced medical products for treating cardiovascular diseases, metabolic diseases, and cancers.

US Center for Biologics Evaluation and Research (CBER) said: “Cellular therapy products include cellular immunotherapies, cancer vaccines, and other types of both autologous and allogeneic cells for certain therapeutic indications, including hematopoietic stem cells and adult and embryonic stem cells. Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use.”

In 1997, US FDA approved the human cell therapy product-Carticel, and various products have since been approved for marketing. Popular research areas are cancers, neurological diseases, and cardiovascular diseases. The cell types used for studies were mostly cord blood hematopoietic stem cells, mesenchymal stem cells, adipose stem cells, and immune cells (T cells, NK cells, dendritic cells).

Presently, most approved hematopoietic stem cell therapy are being processed in laboratories such as Clevecord of Cleveland Cord Blood Center, Duke University School of Medicine’s Ducord, New York Blood Center Hemacord, SSM Health Cardinal Glennon Children’s Hospital’s ALLOCORD, LifeSouth Community Blood Center, and Bloodworks.

Related article: Oncolytic Virotherapy – An Overview 

Gene Therapies’ Prospects

Zolgensma’s (onasemnogene abeparvovec) 2019 marketing approval for patients less than 2 years of age with spinal muscular atrophy (SMA) was a big gene therapy highlight, the one-time treatment hit a record $2.125m price tag. Novartis, the manufacturer of Zolgensma, published new data from its Phase 3 SPR1NT study demonstrating nearly all SMA children treated pre-symptomatically with Zolgensma were able to achieve age-appropriate motor milestones, including sitting independently, standing, and walking. In addition, an analysis of the START, STR1VE-EU, and STR1VE-US studies indicated children with Type 1 SMA achieved or maintained important measures of bulbar function following treatment, including the ability to speak; swallow and meet nutritional needs; maintain respiration.

While Amgen’s Imlygic (talimogenelaher-parepvec, T-Vec) is the first FDA-approved oncolytic viral therapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after the first surgery. The gene therapy is a genetically modified herpes simplex virus type 1, once injected directly into tumors, it replicates inside tumors and produces immunostimulatory protein GM-CSF. Imlygic then causes the tumor to rupture and expire by a process called lysis. The drug is being studied in other trials for improving immune responses against tumor cells.

Written by: Ula Yang, Translated by Fujie Tham

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