Source: Bio Valley
CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy), namely chimeric antigen receptor T cell immunotherapy. This therapy is a new type of cell therapy that has been around for many years but has only been improved and used in the clinic in recent years. It has remarkable curative effect in the treatment of acute leukemia and non-Hodgkin’s lymphoma, and is considered to be one of the most promising tumor treatments. Like all technologies, CAR-T technology has also undergone a long evolutionary process, and it is in this series of evolutionary processes that CAR-T technology gradually matures.
The key to this new therapeutic strategy is an artificial receptor called a chimeric antigen receptor (CAR) that recognizes target cells and is genetically modified Later, the patient’s T cells were able to express the CAR. In human clinical trials, scientists extracted some T cells from patients through a process similar to dialysis, and then genetically modified them in the laboratory to introduce the gene encoding the CAR so that the T cells could express this new receptor. These genetically modified T cells are propagated in the laboratory and then infused back into the patient. These T cells use the CAR receptors they express to bind to molecules on the surface of the target cell, and this binding triggers the production of an internal signal that in turn activates the T cells so potently that they rapidly destroy the target cell.
In recent years, in addition to being used to treat acute leukemia and non-Hodgkin’s lymphoma, CAR-T immunotherapy has also been used to treat solid tumors and autoimmune diseases after improvement. , HIV infection and heart disease and other diseases, has a broader application space. Based on this, in view of the latest progress in CAR-T cell therapy, the editor will make some inventory for readers.
1.Nature: Major progress! Scientists in my country have developed non-viral gene-specific targeting CAR-T cells, and have confirmed in clinical trials that they can safely and effectively treat relapsed/refractory B-cell non-Hodgkin’s lymphoma
In recent years, chimeric antigen receptor (CAR) T cell (CAR-T) therapy has developed rapidly, and it has shown great potential in cancer treatment. However, some limitations remain, including the complex manufacturing process, high production cost, long preparation time and potential safety issues of current CAR-T cell therapies. The use of viruses in CAR-T cell production is an area of concern because disadvantages of this approach include an increased risk of tumor development due to insertional mutations. In addition, specific responses to viral DNA tend to hinder CAR expression, and viral preparation itself often incurs high costs. Although some strategies that do not use viruses, such as the use of transposon systems and mRNA transduction, are being used to generate CAR-T cells, the low homogeneity of CAR-T cells caused by random integration and disruption of CAR expression becomes an additional problem . Recently, several studies have demonstrated that genome editing techniques can be applied to generate locus-specifically integrated CAR-T cells by using adeno-associated virus (AAV) vectors as templates. Furthermore, a preferred non-viral strategy has been proposed to generate T cell products that can correct point mutations and precisely insert T cell receptors (TCRs).
To address the shortcomings of both viral use and random integration, researchers from research institutions including Zhejiang University and East China Normal University in China used CRISPR-Cas9 to develop a non-viral, gene-specific targeting CAR-T cells and confirmed in a Phase 1 open-label, single-arm clinical trial in 8 patients with relapsed/refractory B cell non-Hodgkin lymphoma (r/ rB-NHL) patients with high safety and efficacy. The relevant research results were recently published in the journal Nature with the title of “Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL”.
According to the authors, they are the first in the world to demonstrate the safety and efficacy of a non-viral, gene-specifically targeted CAR-T cell in a clinical trial. By using non-viral CAR-T cells with a CD19-targeting CAR integrated into the PD1 gene (PD1-19bbz CAR-T cells), they found that r/r B-NHL patients treated with these CAR-T cells had Significant safety profile with only a low incidence of mild cytokine release syndrome (CRS) and no neurological toxicity. Their preclinical experiments also showed that PD1-19bbz CAR-T cells were able to efficiently clear tumor cells regardless of whether they highly expressed PD-L1. These findings are also consistent with two previously reported clinical trials, thus further confirming the safety of CRISPR-Cas9 in T cell therapy. At the same time, they observed higher rates of complete remission and durable complete remission. In particular, responses were found in two r/r B-NHL patients with high PD-L1 expression (although one patient later developed CD19-tumor recurrence). Surprisingly, despite the unexpectedly low initial PD1-19bbz CAR-T cell dose (2 x 106 cells per kg body weight), or the proportion of CAR+ cells due to an early and still immature manufacturing process Very low, but 7 out of 8 patients achieved complete remission over a median observation period of 12 months, suggesting that these PD1-19bbz CAR-T cells are more potent in killing tumor cells.
2. Science Sub-Journal: Targeting a pan-cancer epitope of COL6A3 protein by TCR-T cells is expected to treat a series of solid tumors
doi:10.1126/scitranslmed.abo6135
Despite the hype surrounding adoptive T cell therapy, finding therapeutic targets that are consistently expressed across tumor types but not healthy cells remains a challenge. Now, in a new study, researchers from the University of Pennsylvania and Germany’s Immatics Biotechnology (Immatics) have identified a pan-cancer antigen component: COL6A3-FLNV, these two conditions can be satisfied. The findings were recently published in the journal Science Translational Medicine under the title “Quantitative immunopeptidomics reveals a tumor stroma–specific target for T cell therapy”.
In this new study, the authors show that when targeting a pan-cancer antigen component they discovered with T-cell receptor (TCR) T-cell (TCR-T) therapy, Can slow cancer growth in mice. This pan-cancer antigen component is abundant in tumor samples from patients with 11 different types of solid tumors, but rarely in healthy cells, making it a major potential target for T-cell therapy. Now, Immatics plans to apply for an investigational new drug to the U.S. Food and Drug Administration (FDA), hoping to initiate a Phase 1 clinical trial.
With their target in hand, these authors set out to develop TCRs that could recognize this epitope without attacking other peptides. They again used data from the Immatics discovery platform to compare reactivity between tumor cells and normal cells, developed high-affinity TCR-T cells, and injected them into mice that received transplants of human leukemia cells. Cancer growth slowed, and the mice experienced no serious side effects.
3. Nat Med: New study reveals markers of CAR-T cell response in large B-cell lymphoma patients
The treatment of blood cancers has improved dramatically over the past five years, thanks to a new type of cancer immunotherapy called CAR-T cell therapy. The therapy, which involves reprogramming T cells taken from a patient in the lab to kill cancer cells and then infusing them back into the patient, cures about 40 percent of patients with otherwise incurable lymphoma. But there are also people whose cancer comes back or doesn’t respond to this treatment at all.
To understand the molecular mechanisms of this different response, in a study, researchers from the Broad Institute, Dana-Farber Cancer Institute, and Massachusetts General Hospital Blood samples from patients receiving CAR-T cell therapy were studied. They found molecular markers that indicated that patients responded to the treatment, and also identified specific types of immune cells that could lead to cancer recurrence. The findings could one day help doctors choose the best treatments for their patients and help scientists optimize these therapies to improve response rates. The results of the study were published online in the journal Nature Medicine on September 12, 2022, with the title “Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma”.
In the new study, the authors compared large B-cell lymphomas treated with different CAR-T cell therapies — axi-cel and tisa-cel — Blood samples from patients, and the therapies themselves. These two CAR-T cell therapies were the first CAR-T cell therapies approved by the U.S. Food and Drug Administration (FDA) in 2017 and 2018. They both target the CD19 protein on the surface of cancer cells with similar success rates in the clinic.
Utilizing single-cell RNA sequencing, the authors studied how CAR-T cells in these therapies changed over time, from before infusion into a patient’s blood to a week after treatment. They found that these cells had surprisingly different characteristics. After tisa-cel treatment, most of the CAR-T cells in the patient’s blood came from a special type of T cell that helps the immune system’s memory for specific antigens. These T cells were also more abundant in patients who responded well to the therapy compared to those who did not. axi-cel treatment resulted in more admixture of T cell types.
4.Cell Metab: Inhibition of cytophagocytosis can enhance the antitumor activity of endogenous T cells and CAR-T cells, preventing cancer cells from evading immune detection< /p>
doi:10.1016/j.cmet.2022.08.007
The immune system must respond not only to external invaders such as viruses, bacteria and parasites, but also to internal threats such as cancer. However, malignant tumors often overcome the immune system’s defenses and evade immune detection. In a new study, researchers from institutions such as the University of Pennsylvania have uncovered a detailed mechanism by which tumors can evade the immune system and cancer therapies that harness its power, such as genetically engineered CAR- T cells. Relevant research results were published in the journal Cell Metabolism on September 6, 2022, with the title “ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes”.
Image via Cell Metabolism, 2022, doi:10.1016/j.cmet.2022.08.007.
These authors reveal how tumor-derived factors stimulate trogocytosis. When T cells interact with cancer cells, they can sometimes “nibble” on a small patch of the cancer cell membrane. When this small segment of the cancer cell membrane includes an antigen, a molecule specific to cancer, the T cell may begin presenting the antigen on its own cell surface, making it appear to other T cells as a cancer cell.
Previously, cytognathic action was thought to be related to cancer’s ability to thwart anti-cancer immunity, but Fuchs’ team identified this mechanism, showing that T cells exposed to tumor factors experienced a marked decrease in the expression levels of the gene CH25H. It is known that this gene Involved in changing the lipid membrane of the cell and inhibited the fusion of the two cell membranes, which is a necessary process for cytophagocytosis to occur. When they added back a metabolite produced by CH25H, they were able to block Cytophagocytosis. Further characterization of this pathway helped the Fuchs team identify another player, the ATF3 gene, which antagonizes the activity of CH25H. Elimination of AFT3 prevents cytophagocytosis and restores T cells’ ability to kill tumor cells ability.
These new insights not only suggest new targets for anti-cancer therapy, but may have immediate implications for CAR-T cell therapy. Because cytophagocytosis may impair the effectiveness of engineered T cells delivered in CAR-T cell therapy, the authors speculate that blocking this effect could improve CAR-T cell performance. “We thought, ‘Why don’t we use what’s cleverly called ‘armored CAR’ and co-express CH25H in CAR-T cells,” Fuchs said. It turned out to be more efficient than older CAR-T cells. Valid.”
5.Cancer Cell: Myxoma virus and CAR-T cells/TCR-T cells can induce cancer cell suicide, which is expected to be more effective in the treatment of solid tumors< /p>
doi:10.1016/j.ccell.2022.08.001
In a new study, researchers from Arizona State University and Wake Forest University School of Medicine, among others, used the myxoma virus to combine immunotherapy and virotherapy Combined, they offer new hope for patients with refractory cancers. Related research results were published in the journal Cancer Cell on September 12, 2022, with the title “Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance”. The corresponding authors of the paper are Grant McFadden of Arizona State University and Yong Lu of Wake Forest University School of Medicine.
Image via Cancer Cell, 2022, doi:10.1016/j.ccell.2022.08.001.
This approach involves a combination of two approaches, both of which have shown considerable success in some cancers. The study describes how oncolytic virotherapy, a technique that uses an anti-cancer virus, works synergistically with existing immunotherapy techniques to boost immunity and effectively target and destroy cancer cells.
This new study highlights the ability of immunotherapy to break through cancer resistance when combined with viral therapy, particularly using myxoma virus-infected CAR-T cells or TCR-T cells . Myxoma virus can directly target and kill cancer cells, but more usefully can induce an unusual form of T cell-directed cell death, known as suicide. This form of cell death enhances two other forms of programmed cancer cell death induced by T cells, apoptosis and pyroptosis.
During myxoma virus-mediated suicide, other cancer cells in the vicinity of the cancer cell that the therapy targets also attack in a process known as bystander killing. destroyed in the process. This effect could significantly enhance the aggressive eradication effect of this dual therapy on cancer cells, even in notoriously difficult-to-treat solid tumors. Therefore, this combination of myxoma virus and immunotherapy has the potential to turn “cold tumors” that cannot be detected by the immune system into “hot tumors” that immune cells can recognize and destroy, allowing CAR-T cells or TCR- T cells enter the tumor environment, proliferate and activate.
6.Nat Med: CD19-targeting CAR-T cell therapy is expected to treat refractory lupus erythematosus
While there is no cure for lupus erythematosus and existing treatments don’t work for many of the 1.5 million lupus patients in the United States, a new study suggests a cancer therapy may Relieves difficult-to-treat lupus erythematosus. The results of the study were published online in the journal Nature Medicine on September 15, 2022, with the title “Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus”.
This small study included five people with severe lupus erythematosus, a disease that affects multiple organs, such as the kidneys, heart, lungs and joints, and does not respond to standard treatments. About three months after a single treatment, the patient’s symptoms improved, including remission of organ involvement and disappearance of disease-related autoantibodies. What’s more, they don’t require any additional treatment.
Corresponding author Dr. Georg Schett of the University of Erlangen-Nuremberg, Germany, said, “Severe [lupus erythematosus] is very sensitive to CAR-T cell therapy and [patients] can enter long-term period of drug-free remission.”
7. Cancer Cell: Major Progress! New research develops VIPER CAR-T cells that can be turned on or off as needed, promising safer cancer treatment
doi:10.1016/j.ccell.2022.08.008
To make the groundbreaking CAR-T cell therapy less risky for patients, Wong and his team are working to build a safety switch built into the CAR-T cell design. In a new study, the authors reveal a new type of CAR-T cells that can be turned on or off, potentially preventing cell activation before serious side effects occur. The relevant research results were published online in the journal Cancer Cell on September 8, 2022, with the title of “High-performance multiplex drug-gated CAR circuits”.
Image via Cancer Cell, 2022, doi:10.1016/j.ccell.2022.08.008.
Their new system is called VIPER (Versatile ProtEase Regulatable) CAR-T cells. The designed VIPER CAR-T cells can be controlled by giving patients an antiviral drug that disrupts cell activity, reducing the safety concerns posed by traditional CARs. “We see it as the next generation of this type of therapy,” Wong said.
In all CAR-T cells, one part of the CAR sticks out of the cell membrane, while the other part is inside the cell. The part that sticks out of the cell membrane binds to cancer antigens, which then activate T cells and destroy cancer cells. VIPER CAR-T cells insert a special protein chain near the CAR. The authors constructed two different systems — one that was turned on when VIPER CAR-T cells were transferred back to the patient, and the other that was turned off. The two systems work in slightly different ways, but both can be turned off or on by a patient taking an FDA-approved drug commonly used to treat hepatitis C.
Li Huishan, co-first author of the paper and a postdoc in Wong’s lab, said, “This is the most exciting part of this study, which is that the antiviral drug has been approved by the FDA.” When a drug is administered, the drug molecule interacts with the inserted protein chain to initiate a series of reactions in the cell that disengage it, or activate it, depending on which system is used.
8.eLife: Scientists uncover possible pathway to improve T-cell therapy
doi:10.7554/eLife.79508
Recently, in a research report entitled “Enhancing and inhibitory motifs regulate CD4 activity” published in the international journal eLife, scientists from the University of Arizona School of Medicine and other institutions discovered through research New information on the inner workings of the body’s immune system may have profound implications for the later development of novel T-cell therapies against cancer and other diseases.
In the article, the researchers took a unique evolutionary approach to the immune system by analyzing the way T cells changed or remained the same over time, focusing on the evolution of CD4 and features were thoroughly researched. Dr. Kuhns said this study may help us draw a blueprint for how CD4 molecules cooperate with T cell receptors and guide T cells naturally; CD4 molecules play a very equal role in antigen recognition and T cell activation. .
Related findings may help researchers paint a more accurate evolutionary blueprint for the mechanisms within CD4, leading to a more powerful version of T-cell therapy, chimeric antigen receptor (CAR) T Cell therapy is now used to treat many types of cancer. In this paper, the researchers examined the possibility of genetically engineering modified 5-module CAR-T cells as a treatment for type 1 diabetes.
The researchers analyzed the CD4 molecule in a variety of samples from fish to humans to explore the molecule’s evolution over 400 million years, and then they identified a very important molecule for mammals. “Specific regions of a particular CD4 molecule; we looked at which amino acids in these proteins changed and which amino acids in these proteins remained the same, which is important for studying protein function,” said Dr. Van Doorslaer. The researchers then discovered a conserved amino acid sequence called motifs and revealed the molecular mechanism by which these motifs enhance or inhibit the activity of CD4 molecules, they designed genes carrying mutant motifs and introduced them into into a T-cell system, followed by observing the protein’s response, where it is in the cell and what it interacts with, and how it affects signaling events and outcomes; it turns out that different combinations of motifs lead to varying degrees of up and down.
9.JAMA Oncol: Detection of NfL protein levels in blood predicts which cancer patients are more likely to develop neurotoxicity after CAR-T cell therapy
doi:10.1001/jamaoncol.2022.3738
Cell-based immunotherapy — CAR-T cell therapy — has revolutionized the treatment of several cancers. The therapy uses genetically engineered T cells to target and attack certain types of leukemia and lymphoma. While it can eliminate cancer in some patients who would otherwise die from it, it also comes with a risk of a host of side effects, some of which can affect brain function and can even be life-threatening.
In a performance study, researchers from Washington University School of Medicine in St. Louis found that a simple blood test performed before CAR-T cell therapy began could determine which patients were in CAR-T cell therapy. Neurotoxic side effects are prone to occur in the days and weeks following T-cell therapy. When they analyzed blood samples from patients before, during and after CAR-T cell therapy, they found that levels of a protein called neurofilament light chain (NfL) were higher in patients with neurotoxic complications . High levels of NfL were present even before treatment began, and its levels remained high throughout treatment and for a month after treatment. The results of the study were published online in the journal JAMA Oncology on September 1, 2022, with the title “Assessment of Pretreatment and Posttreatment Evolution of Neurofilament Light Chain Levels in Patients Who Develop Immune Effector Cell–Associated Neurotoxicity Syndrome”.
Relationship between nerve fiber light chain (NfL) levels and immune effector cell-associated neurotoxicity syndrome. Image via JAMA Oncology, 2022, doi:10.1001/jamaoncol.2022.3738.
This new study may help physicians predict these life-threatening side effects and enable them to start giving neurotoxicity-reducing therapy early in patients receiving CAR-T cell therapy. It also opens the door to developing ways to prevent or reduce the risk of these side effects before CAR-T cell therapy begins.
10.Blood Cancer Discov: Specific components of the tumor immune microenvironment may influence the efficacy of BCMA CAR-T cells against myeloma
doi:10.1158/2643-3230.BCD-22-0018
In a new study, researchers from Emory University and the University of Pennsylvania find that the tumor immune microenvironment has a more diverse baseline T cell repertoire, less immune Myeloma patients with marked changes in markers of cell exhaustion and immune cell populations were more likely to experience longer progression-free survival after receiving BCMA-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy ( progression-free survival, PFS). The results of the study were published online on August 26, 2022 in the journal Blood Cancer Discovery with the title “Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma”.
In the new study, the authors analyzed 28 pre- and post-treatment bone marrow samples from patients in a previously reported Phase I clinical trial led by Cohen and colleagues have a clinical response to CAR-T cell therapy targeting BCMA. They found that in patients with longer progression-free survival, the proportion of T cells in the bone marrow increased after treatment, while the proportion of bone marrow cells decreased. These changes were not observed in patients with shorter progression-free survival. Dhodapkar suggested that a higher proportion of myeloid cells may have contributed to cancer recurrence in these patients by promoting cancer growth and/or suppressing anti-tumor immune responses.
These authors also found that post-treatment CAR-T cells (i.e. CAR-expressing T cells) and non-CAR T cells (i.e. non-CAR-expressing T cells) from patients with longer progression-free survival T cells) have distinct genomic signatures with lower expression of immune checkpoint genes and other genes associated with T cell exhaustion compared with patients with shorter progression-free survival. In addition, T cells from patients with longer progression-free survival had higher expression of genes associated with bone marrow retention.
Baseline characteristics were also associated with progression-free survival: greater T-cell receptor diversity was observed in pretreatment bone marrow samples from patients with longer progression-free survival, higher Tumor expression of interferon-responsive genes and mature plasma genes, as well as genes associated with epithelial-to-mesenchymal transition (EMT), were lower in tumors.
11.Blood Adv: Higher doses of CAR-T cell product tisagenlecleucel resulted in higher survival rates within the approved clinical dose range
The U.S. Food and Drug Administration (FDA) approved tisagenlecleucel — a chimeric antigen receptor T-cell (CAR-T) product — according to a new study Across the dose range, young adults who received the comparative dose had significantly better one-year survival rates than those who received lower doses in the range. The findings were recently published in the journal Blood Advances in a paper titled “Higher doses of tisagenlecleucel associate with improved outcomes: a report from the pediatric real-world CAR consortium.”
In the new study, the authors analyzed overall survival, no Event survival and recurrence-free survival. They found that compared with patients who received lower doses (0 to 1.3 million CAR-T cells/kg), patients who received higher doses within the approved range (2.4 million to 5.1 million CAR-T cells/kg) had better Survival rates were significantly higher on all three measures. In the highest dose group, 86% of patients were still alive after one year, compared with 59% in the lowest dose group. These authors did not observe any signs of increased toxicity or safety concerns with higher doses.
These findings suggest that administering higher doses of tisagenlecleucel within the approved range may help achieve more effective long-term responses without increasing the risk of toxicity. Dr. Schultz said, “A lot of effort has been focused on the complex design and development of next-generation CAR-T cell therapies. This new study was designed to explore whether clinical manipulation using our currently approved tisagenlecleucel could lead to incremental advances in the field. Progress.
12.BMC Cancer: Killing tumor cells!—-A non-viral mcDNA-mediated bispecific CAR T cell
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and its adoptive immunotherapy deserves investigation. CD133 is a cancer stem cell (CSC) antigen that, together with glypican-3 (GPC3), has been shown in HCC cellsare highly expressed, and they can be used as targets for the generation of chimeric antigen receptor (CAR) T cells. However, there are “off-target” toxicity in CAR T cell therapy, and there are limitations such as low transfection efficacy and weak anti-tumor ability.
Recently, a research team from Zhongshan Hospital Affiliated to Fudan University in China has conducted research on a non-viral mcDNA-mediated bispecific CAR T cell to study its ability to inhibit tumor proliferation ability.
In this study, peripheral blood was obtained from healthy donors and T cells were isolated by density gradient centrifugation. The researchers used an electroporation system to deliver anti-CD133 and anti-GPC3 single-chain fragment variant (scFv) constructs as target genes into T cells. The cell membrane is opened by a transient current effect, and the target gene is delivered into the cell by a non-viral microcircular DNA (mcDNA) vector. Flow cytometry and western blotting were used to examine whether the two scFvs were transfected simultaneously and the transfection efficacy of this bispecific CAR-T cell generation method. The in vitro and in vivo tumor suppressive efficacy of CAR T cells was then tested by CCK-8 assay and HCC xenograft mouse model, respectively. CoG133-CAR T cells containing both CD133 and GPC3 antigen recognition sites are effector cells. CD133-CAR T cells and GPC3-CAR T cells were defined as the single-targeting control group, and normal T and mock T cells were defined as the blank control group.
mcDNA vectors accommodate two successfully transfected target gene constructs to generate bispecific CAR T cells. Gene-level and protein-level detection methods confirmed that CoG133-CAR T cells had strong transfection efficiency and exhibited antigen-binding ability of CD133 and GPC3. Compared with single-target CAR T cells or control T cells, CoG133-CAR T cells had enhanced depletion efficacy against CD133 and GPC3 double-positive HCC cell lines in vitro and in HCC xenograft mice in vivo. Hematoxylin and eosin (H&E) staining indicated the absence of lethal “off-target” combinations on CoG133-CAR T cells and major organs.
This study shows that the generation of bispecific CAR T cells from a non-viral mcDNA vector is more efficient and safe. CoG133-CAR T cells enhance tumor suppressive ability through dual antigen recognition and internal activation. It provides an innovative strategy for CAR-T therapy of hepatocellular carcinoma (even solid tumors).
13.JCI: Scientists develop a new technique that can determine the success of CAR-T immunotherapy or may improve the treatment of human lymphoma
doi:10.1172/JCI159402
One of the most critical battles in the human war against cancer is at the cellular level, as T cells from the immune system can be altered in the lab to attack cancer cells, This type of immunotherapy, called chimeric antigen receptor T-cell therapy (CAR-T cell therapy), has emerged as a way to save cancer patients, successfully controlling tumors for a decade or more. Recently, in a research report entitled “Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses” published in the international journal Journal of Clinical Investigation, scientists from the University of Houston and other institutions passed the Research has uncovered a new method that may help determine which patients are likely to respond to CAR-T cell therapy, saving time in treating human lymphomas that respond most strongly to this type of immunotherapy. It may be a very valuable research result, because not all patients will respond to CAR-T cell therapy, and some patients will experience serious side effects.
To determine optimal patient outcomes, Navin Varadarajan, MD, et al. studied the dynamic interactions between T cells and tumor cells, a discovery that revealed The association between a ligand molecule for CD58 and a protein called CD2 on T cells that communicate with each other may activate CD2 and turn it into a cancer cell killer. Varadarajan said that as a ligand for CD2, CD58 is expressed at high levels in the tumors of lymphoma patients who respond well to CAR-T cell therapy. For this reason, we found that CD2 on T cells may be related to directional migration of cells. And the interaction between CD2 on T cells and CD58 on lymphoma cells may accelerate killing and continue the killing effect.
In this study, researchers used the TIMING method (Timelapse Imaging Microscopy In Nanowell Grids) to dissect the composition of patient infusion products and tumors The dynamic interaction between the , interaction, lethality, and survival conditions. By analyzing thousands of single mechanisms of interaction between T cells and tumor cells, the researchers identified an important interaction between CD2 and CD58. The obtained tumors were analyzed for staining, and the researchers pointed out that patients with CD58 expression in tumor tissue may have a stronger response to CAR-T cell therapy than patients whose tumors did not express CD58.