Year-end inventory: CAR-T cell weight study interpretation

The key to this new treatment strategy is to identify artificial receptors called chimeric antigen receptors (CAR) in the target cells, and after genetic modification, the patient's T cells are able to express the CAR.
In human clinical trials, scientists extracted T-cells from patients through a dialysis-like process and then genetically modified them in the lab to import the GENES that encode the CAR so that the T-cells could express the new subject.
these genetically modified T-cells are proliferated in the lab and then perfused back into the patient.
these T-cells use the CAR subjects they express to bind to molecules on the surface of the target cell, which triggers an internal signal that then activates the T-cells so powerfully that they quickly destroy the target cells.
In recent years, CAR-T immunotherapy has been used to treat diseases such as solid tumors, autoimmune diseases, HIV infections and heart disease, in addition to acute leukemia and non-Hodgkin's lymphoma.
based on this, the editor-in-chief has made an inventory of the latest advances in CAR-T cell therapy in 2020 to reach out to readers.
1.Science and Cell Sub-Journal: Developing "Intelligent" Cell Therapy for Cancer with Big Data Doi:10.1016/j.cels.2020.08.002; doi:10.1126/science.abc6270 Finding drugs that kill cancer cells while keeping normal tissue unsalted is the top goal of oncology research.
in two new papers, researchers from the University of California, San Francisco, and Princeton University suggest complementary strategies for solving this conundrum with "smart" cell therapy: these live cell drugs remain inert unless activated by a group of proteins that appear only in cancer cells at the same time.
the biology of this universal approach has been explored for several years by Dr. Wendell Lim and his colleagues in the labs of the Cell Design Program at the University of California, San Francisco, and the Synthetic Immunology Center sponsored by the National Cancer Institute.
, however, add a powerful new dimension to this by combining cutting-edge therapeutic cell engineering with advanced computational methods.
in the first paper, published In the September 23, 2020 issue of cell Systems, entitled "Companiesman Power of Combinatorial Antigen Acknowledge in Cancer T Cell Therapies," members of Lim Labs teamed up with Dr. Olga G. Troyanskaya, a computer scientist at Princeton University's Louis-Sigler Institute for Integrated Genomics.
using machine learning, they analyzed a large database of thousands of proteins found in cancer and normal cells.
, they screened millions of possible protein combinations to create a list of protein combinations that could be used to precisely target only cancer cells, not normal cells.
in a second paper, published in the November 27, 2020 issue of Science, entitled "Precise T cell development programs by transcriptionary linking multiple receptors," Lim and his colleagues then demonstrated how these calculated protein data can be used to drive the design of effective and highly selective cancer cell therapies.
: Clinical trials show that CAR-T cells targeting GD2 are promising to treat neuroblastoma doi:10.1126/scitranslmed.abd6169 in a new In the study, researchers from research institutions such as Great Ormond Street Children's Hospital in the UK and University College London developed a new CAR-T cell therapy designed to target cancerous tumours, showing promising early results in children with neuroblastoma, a rare childhood cancer.
study was published in the Journal of Science Translational Medicine on November 25, 2020 under the title "Antitumor activity on-off target-tumor toxicity of GD2-chimeric antigentor recep recep T cells with neuroblastoma".
in this principled validation study, the authors genetically modified the patient's own T-cells, an immune cell, to recognize and kill neuroblastoma cells.
12 children with relapsed or resuscient neuroblastoma received the treatment as part of a Phase I clinical trial funded by Cancer Research UK.
study was one of the first to demonstrate that CAR-T cells can rapidly recede solid cancer.
the beneficial effects last only a short time, it provides important evidence that this particular CAR-T cell therapy could be used as a future treatment for solid cancer in children.
3.Science Sub-Journal: Transcription factor STAT5 continuous activation can improve the anti-tumor immune response of CAR-T cells doi:10.1126/sciimmunol.aba5962 Using the overreactive cell therapy of inlay antigens (CAR) T cells (CAR-T) to show strong anti-tumor immunity, but T-cell failure may impair their efficacy.
presence of multi-functional CD4 plus T cells is usually associated with good anti-tumor immunity.
previously found that IL-7 processing induces the activation of multi-functional CD4-T cells that produce multiple cytokines.
a new study, researchers from research institutions such as the University of Augusta in the United States report that the continuous activation of the transcription factor STAT5 in tumor-specific CD4 plus T cells drives the production of multifunctional T cells.
results were published in the October 30, 2020 issue of the Journal of Science Immunology under the title "Persistent STAT5 activation reprograms the epigenetic landscape in CD4 plus T cells to drive polyfunctionality and antitumor immunity."
they found that the hetero-expression of the component active form of STAT5A in mice (constitutive active form of murine STAT5A, CASTAT5) enabled tumor-specific CD4-T cells to amplification robustly, effectively immerse tumors, and trigger anti-tumor CD8-T-cell reactions in the CD4-T cell over-transfer model system.
combined ethonomic genomics and transcriptomic analysis showed that CASTAT5 induced chromosomal remodeling throughout the genome in CD4 and T cells, and established a unique landscape of oscic genetics and transcription.
sequencing analysis of single-cell RNA further identified a sub-group of CASTAT5 transduction CD4 plus T cells with molecular characteristics indicating multifunctional T-cell progeny cells.
the researchers found that in mouse models of B-cell lymphoma, the over-transfer of T cells that together express CASTAT5 and chimic antigen-subject (CAR) targeting CD19 led to the production of multifunction CD4 plus CAR-T cells.
findings make CASTAT5 potentially therapeutic.
4.Nat Med: Phase I clinical trials have shown that dual-specific CD19/CD20 CAR-T cells are expected to treat relapsed B-cell malignancies doi:10.1038/s41591-020-1081-3 Inlay antigen-subject (CAR)T-cell (CAR-T) therapy is considered a breakthrough technique for treating multiple types of tumors.
non-Hodgkin's lymphoma (Non-Hodgkin lymphoma, NHL) and chronic lymphocytic leukemia (CLL) are two CD19-positive B-cell cancers that have been treated with CAR-T cells that recognize CD19.
CD19 is a classic molecule located on the surface of B cells, the method of targeting CD19 only will cause its expression to decline and often fail to treat.
to overcome this limitation, Shah et al. used an automated cell processing platform in a new study to develop dual-specific CAR-T cell therapy targeting CD19 and CD20( CD19/CD20 CAR-T cells).
study is a Phase 1 dose increment and enlargement clinical trial.
in this clinical trial, these dual-specific CAR-T cells were used to treat NHL or CLL patients.
, this clinical study included 26 patients who had previously experienced multiple failures in anti-B cell therapy.
, this dual-specific CAR-T cell therapy is considered safe for treatment.
64% and 32% of patients had cytokine release syndrome and neurotoxicity, respectively.
response rate was 82%, and 12 patients who received high doses of freshly prepared CD19/CD20 CAR-T cells responded.
, 43% of patients receiving cryogenic preservation cd19/CD20 CAR-T cells experienced treatment failure.
suggests that the use of freshly prepared CD19/CD20 CAR-T cells may be the key to successful treatment.
, three patients did not respond to the treatment.
respondents showed high levels of circulating CAR-T cells, suggesting the presence of antigen stimulation, but the lethal activity of these CAR-T cells decreased significantly.
5. Heavy! Scientists have successfully created a new type of CAR-NKT cell, or promising to develop a new type of immunotherapy to treat solid tumors doi:10.1038/s41591-020-1074-2 Natural Killer T-Cells (NKT) is a class of immunocellular cells that have been shown to have potential anti-cancer properties in mouse tumor models, and now researchers hope to use NKT cells to develop a new type of immunotherapy to treat cancer patients.
, scientists from institutions such as Baylor College of Medicine used chimed resistance in a recent study published in the international journal Nature Medicine entitled "Anti-GD2 CAR-NKT cells with patients with relapsed or refractory neuroblastoma: an interim analysis" The primary subject (CAR) is genetically modified for human NKT cells, which specifically identifies and attacks neuroblastoma (a childhood cancer), and the modified NKT expresses interletin-15 (IL-15), a natural protein that supports the survival of NKT cells. In the
study, researchers published the interim results of an ongoing clinical trial that showed that modified NKT cells were safe and implantable into tumors, and that in one of the three patients in the trial, the body successfully induced an objective response to bone metastasis lesions.
The earliest CAR modified cells were immune T cells, and CAR T cells have been shown to be effective in treating leukemia and lymphoma, but scientists have faced some challenges in trying to treat solid tumors with CAR T cells, and preclinical studies have shown that NKT cells can provide a new way to help enhance CAR-oriented cancer immunotherapy.
researcher Professor Leonid Metelitsa said that in addition to being effective in protecting against tumors in mouse model bodies, the presence of NKT cells in solid tumors was directly related to beneficial outcomes in cancer patients.
previous studies have shown that NKT cells have broad-spectrum anti-tumor activity.
, for example, these cells can migrate to tumor spots, where they kill tumor-related macrophages, which are immune cells that promote tumor growth and metastasis.
addition, the activation of NKT cells indirectly promotes the anti-tumor immune response mediated by NK cells and T cells.
6.JCI: Significant progress! THE DEVELOPMENT of CAART cell therapy, which promises to treat autoimmune diseases such as mucosal common herpes doi:10.1172/JCI138416 In a new study, researchers from the University of Pennsylvania in the United States have found that a powerful new method for treating mucosal tinge tinges (pemphigus vulgaris, PV) in animal models is safe and effective.
Based on their experience with a cutting-edge anti-cancer strategy called chisellular antigen (CAR-T) therapy, car-T cell therapy is a genetic modification of the patient's own T-cells and then infusion of these genetically modified T-cells back into the patient to attack cancer cells.
similar genetic modification can lead T cells to selectively destroy the self-reactive B cells that cause mucous membrane PV.
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