Cell and Gene Therapy: a New Direction for Innovative Therapies

Cell therapy

Cell therapy is the introduction of new cells into a tissue to stimulate the body’s ability to heal itself and repair or rebuild a strong immune system in order to treat disease.

Cell therapy is mainly divided into stem cell therapy and immune cell therapy.

Stem cells therapy

Stem cells have the ability to self-renew. Patients’ autologous stem cells are easy to obtain and have a low risk of cancer. At the same time, there is no immune rejection or ethical controversy, so they are more widely used in clinical practice. The types of stem cells used in clinical treatment mainly include bone marrow stem cells, hematopoietic stem cells, neural stem cells, and so on.

Stem cell therapy has been widely used in the treatment of various clinical diseases, including blood diseases, organ transplantation, cardiovascular system diseases, liver diseases, nervous system diseases, tissue trauma and others.

Immune cell therapy

Immune cells are the cells which involved in or related to the immune response, including NK cells, T cells, B cells, macrophages, etc. At present, immune cell therapy is mainly used in the treatment of cancer. According to the different immune cells used, it can be divided into cytokine-induced killer cell (CIK) therapy, API biological immunotherapy, DC-CIK cell therapy, natural killer cell (NK) therapy, etc.

The application of immune cell therapy in cancer therapy is mainly achieved by adoptive immunotherapy. Adoptive immunotherapy means the separation of immunoactive cells from tumor patients, amplification and functional identification in vitro, and then retransfusion to patients, so as to directly kill tumor or stimulate the body’s immune response to kill tumor cells.

Adoptive immunotherapy falls into three main categories:

• Using tumor-infiltrating lymphocytes (TIL) isolated from a patient’s tumor, expanded in the laboratory and then reinjected into the patient;
• harvesting T cells from patients and engineering to express tumor antigen-specific T cell receptors (TCR) so that T cells can recognize and attack tumor cells that express this antigen
• Similar to TCR, it constructs a chimeric antibody receptor (CAR) on T cells, allowing immune T cells not only to specifically recognize cancer cells, but also to activate T cells to kill cancer cells.

Currently, CAR-T is the only adoptive immunotherapy approved by the FDA. TIL and TCR therapy can only target and eliminate cancer cells that present their antigens under specific conditions (when the antigens bind to the major histocompatibility complex or MHC).The main advantage of CARS is that they can bind to cancer cells even without presenting them to the surface via MHC, leaving more cancer cells vulnerable to attack. However, CAR T cells can only recognize antigens that are expressed naturally on the cell surface and thus have a smaller range of potential antigen targets than TCR.

Gene therapy

In a broad sense, gene therapy refers to the treatment of a disease by correcting or compensating for abnormal genetic defects. As the basic unit of genetic material, gene can control the expression of inherited characters and regulate the activity. There are a number of symptoms that occur when a genetic abnormality occurs in humans. The most typical symptom of a genetic mutation is sickle anemia. Gene therapy involves introducing therapeutic genes into patients by means of gene transfer or gene regulation. The expression of normal genes can treat the patient’s disease.

Since 2012, gene therapy has an important paradigm shift: genetic complement strategy becomes more comprehensive, gene editing, target gene recombination, antisense oligonucleotide induced exons bouncing and RNA interference in clinical, that simple increase function normal genes to improve the dominant disease is very important.

Gene therapy can be divided into two categories: in vitro therapy and in vivo therapy. The pipeline for gene therapy in vivo and in vitro is evenly split, with viruses still the most commonly used gene vector. The majority of in vitro cell gene therapy uses autologous cells, which account for 58% of the in vitro gene therapy pipeline, and only 14% of the pipeline uses allogeneic cells. This is mainly because allogeneic cells reduce the time and stress of treatment for patients, but there are problems with the immune response.

For both in vivo and in vitro treatments, 59% of the pipeline used viral vectors, while only 13% used non-viral vectors such as plasmids, mRNA, and liposomes. Among viral vectors, adeno-associated virus (AAV) has been widely used in gene therapy due to its characteristics of low virulence, high transduction rate, controllable cost and low insertion risk.