Literature Review on Research progress in the field of cell therapy (2015-2019)
In September 2015, scientists from the University of Pennsylvania successfully used CAR-T cell therapy to treat patients with advanced refractory multiple myeloma. After high-dose melphalan and autologous transplantation, CTL019 was injected. The condition was sustained and completely relieved.
In a study published in Clinical Investigation in May 2016, researchers from the Fred Hutchinson Cancer Research Center successfully used experimental T-cell therapy to slow down 93% of patient's condition with malignant leukemias. This new treatment is expected to improve the prognosis and quality of life of patients with malignant leukemia. In June, Posey et al. published in Immunity magazine that they successfully used the new CAR-T immunotherapy for a series of solid tumors. In the article, the researchers constructed CAR-T cells expressing specific CARs, which specifically recognize truncated sugar molecules on mucin 1 (MUC1) when injected back into these CAR-T cells. After leukemia or pancreatic cancer in mice, tumors in mice have shrunk and their survival has increased. In a study published in the journal Stem Cell Reports in July, scientists from Peking University found a new target for the treatment of bone defect diseases using adipose stem cells. They found a microRNA can facilitate osteogenesis by affecting the regulatory networks of fat stem cells. Relevant results provide a new direction for the use of adipose derived stem cells for treating osteoporosis and other diseases.
In October 2017, scientists from the University of Pennsylvania in the United States successfully used CAR-T cell therapy to combat HIV infection. In the article, researchers developed a new strategy that could potentially engineer a patient's own genes of immune system cells to fight HIV infection. In a study published in the journal Nature Medicine in November of the same year, scientists from Stanford University School of Medicine developed a new type of novel CAR that targets CD22 surface molecules. In phase I clinical trials, it was found that this new type of CAR-T cell immunotherapy is expected to treat B-cell acute lymphoblastic leukemia.
In March 2018, a research report published in Science Translational Medicine, scientists from the University of Pennsylvania succeeded in using the mesenchymal stem cells in the gums to accelerate wound healing. In the article, the researchers clarified the interdental space. Mesenchymal stem cells accelerate the new molecular mechanism of tissue repair; the researchers said that they can harvest mesenchymal stem cells from the gums and use them in the clinic. Later, it is expected to use these cells to reduce the formation of scars in the body tissues, improve wound healing, and even for the treatment of a variety of inflammatory and autoimmune diseases.
In a study published in Cell in June 2018, scientists from the University of Pennsylvania succeeded in promoting CAR-T cell therapy for the treatment of acute myeloid leukemia by studying the use of CRISPR/Cas9 to transform hematopoietic stem cells. In July, Li et al. published a report in Cell Stem Cell that they have successfully developed CAR-NK cell therapy, which is expected to become the new darling of the immunotherapeutic community. In this article, researchers found that natural killer cells (NK cells) cultured in pluripotent stem cells and modified in a similar manner to CAR-T cells are highly resistant to ovarian cancer in a mouse model. In a September issue in Nature, researchers from the University College London found that special stem cells in the blood can produce endothelial cells, and the resulting endothelial cells can be added to the blood vessel wall. This unique stem cell helps repair damage to blood vessels, is expected to treat heart disease and systemic circulatory disease. In November, scientists from Japan are the first in the world to use IPS cells to successfully treat patients with Parkinson's disease. In this paper, researchers have used a novel technology to transform ips cells into neuronal precursor cells (ie, dopamine precursor cells) that produce neurotransmitter dopamine, which is expected to treat Parkinson's disease.
In a study published in Nature February 2019, scientists from the United States found a way to resist T cell failure and make CAR-T cell therapy more effective. The researchers found a family of proteins called Nr4a transcription factors play an important role in regulating genes involved in T cell failure. By studying mouse models, the researchers confirmed that treatment with CAR-T cells lacking the Nr4a transcription factor can make small tumors in the rat body shrink and improve their survival rate. In a study published in the March issue of Science Translational Medicine, Kansal et al. showed that the use of CAR-T cells is expected to treat lupus. Using genetically modified T cells that target the chimeric antigen receptor (CAR) that targets CD19, the researchers successfully killed B cells in two lupus mouse models, which cleared the autoantibodies produced by B cells and prolonged the life of the mouse model.
In April 2019, scientists from institutions such as Boston Children's Hospital in the United States published a report in the PNAS magazine that the use of nano-antibody-based CAR-T cells is expected to treat patients with solid tumors. In the article, the researchers said that the mini-antibodies from alpaca can be further shrunk to form so-called Nanobodies, which may be expected to help solve a problem in cancer research that allows CAR-T cell therapy to play a role in solid tumors.
The above is a collection of the major research results that scientists have brought to the field of cell therapy in the past decade. After reading this article, I believe that everyone can have a general picture on the status quo of cell therapy. Hopefully more gratifying results in this field can be achieved in the future.
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