【1】NEJM: Small clinical trials show that CAR-T cells targeting GPRC5D can effectively treat myeloma
2022-10-25 reported that in a new study, researchers from Memorial Sloan Kettering Cancer Center (MSK), Dana-Farber Cancer Institute and Roswell Park Comprehensive Cancer Center pointed out that a A CAR-T cell therapy that uses genetic modification of T cells in the immune system to target a somewhat mysterious cellular protein, the GPRC5D antigen, emerged in the first clinical trial of patients with multiple myeloma. achieved remarkable results. The relevant research results were published in the NEJM journal on September 29, 2022, with the title of the paper "GPRC5D-Targeted CAR T Cells for Myeloma".
"This is a novel cell therapy for multiple myeloma, and in this first small study, patients showed strong responses," said co-corresponding author Dr. Renier Brentjens, associate director of the Roswell Park Comprehensive Cancer Center. rates, even in patients previously treated with other CAR-T cells targeting another antigen, BCMA. This is a proof-of-principle study, but these results suggest that not just a single CAR-T cell population was infused, but This provides a rationale for using multiple CAR-T cell populations that may target different proteins on the surface of tumor cells."
Original: doi:10.1056/NEJMoa2209900.
【2】Nat Med: Dual-targeted CAR NK cells are expected to prevent NK cell failure and tumor escape
2022-10-25 reported that in a new study, researchers from the University of Texas MD Anderson Cancer Center developed a new method: in addition to genetically modifying natural killer cells (NK cells) to make them In addition to expressing a chimeric antigen receptor (CAR) that recognizes tumor antigens, they are further genetically modified to express a CAR that acts as a logic gate that inhibits NK cell self-recognition, thus making this dual Targeting CAR NK cells requires two signals to kill target cells. In preclinical experiments, this next-generation CAR NK cell improved tumor specificity and enhanced antitumor activity by overcoming a process that leads to NK cell dysfunction and tumor recurrence. The relevant research results will be published in the journal Nature Medicine in October 2022. The title of the paper is "KIR-based inhibitory CARs overcome CAR-NK cell trogocytosis-mediated fratricide and tumor escape".
The new study demonstrates that a normal physiological process called "trogocytosis" leads to tumor escape and CAR NK cell post-therapy responses by leading to loss of tumor antigens, CAR NK cell dysfunction and cannibalism bad.
In cytocytosis, surface proteins from target cells are transferred onto the surface of immune cells such as NK cells or T cells to regulate the activity of the latter. Using preclinical models, first author Ye Li, a graduate student in Rezvani's lab, and colleagues found that CAR activation promotes cytotoxicity, which leads to the transfer and presentation of tumor antigens on the surface of CAR NK cells.
Original: doi:10.1038/s41591-022-02003-x.
[3] Gilead Yescarta was approved by the European Union: the first CAR-T cell therapy for the second-line treatment of B-cell lymphoma (DLBCL/HGBL)!
2022-10-25, Kite, a T cell therapy company under Gilead Sciences (Gilead), recently announced that the European Commission (EC) has approved the CD19 CAR-T cell therapy Yescarta (axicabtagene ciloleucel): for the second-line treatment of diffuse large B cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). The specific population is: adult patients with DLBCL and HGBL who are refractory to first-line chemoimmunotherapy or who have relapsed within 12 months after completing first-line chemoimmunotherapy. It is worth mentioning that Yescarta is the first CAR-T cell therapy approved in Europe for first-line treatment ineffective patients (DLBCL and HGBL), marking the first therapy superior to standard care in nearly 30 years, and will be the most common Non-Hodgkin lymphoma (NHL) offers an important additional treatment option.
【4】Cancer Cell: It is reported that the loss of BATF can improve the anti-tumor activity of CAR-T cells
Reported on 2022-10-25, the team of Wang Haoyi, Institute of Zoology, Chinese Academy of Sciences, State Key Laboratory of Stem Cell and Reproductive Biology, and Beijing Institute of Stem Cell and Regenerative Medicine published a paper entitled Depletion of BATF in CAR-T cells on Cancer Cell The latest research results of enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells. In order to better explore the process and mechanism of T cell exhaustion, this study obtained a human primary CAR-T cell exhaustion model with typical exhaustion characteristics in vitro by reducing the ratio of CAR-T cells and tumor cells and prolonging the co-culture. In order to discover new regulators of T cell exhaustion, this study screened candidate genes based on this model, and found that knocking out the transcription factor BATF could significantly improve the anti-tumor activity of CAR-T cells in vivo and in vitro. Subsequent mechanistic studies found that BATF directly targets multiple key genes associated with exhaustion and up-regulates their expression, while BATF targets and regulates the expression of effector and memory T cell-related genes. Therefore, knocking out BATF improves the ability of CAR-T cells to resist exhaustion while allowing CAR-T cells to generate more central memory cell subsets, thereby improving the efficacy of CAR-T cells in treating solid tumors.
[5] Nat Commun: Scientists are expected to overcome the molecular mechanism of breast cancer resistance to therapy
2022-10-20 report, recently, in a research report entitled "Targeted immunotherapy against distinct cancer-associated fibroblasts overcomes treatment resistance in refractory HER2+ breast tumors" published in the international journal Nature Communications, from Spanish Cancer Network Biomedical Research Scientists from institutions such as the center have revealed the molecular mechanism behind the above process through research.
In the article, researchers identify a new way that may overcome the way tumors protect themselves and allow the immune system to act on tumor cells, using an in vitro model that includes living cells from breast cancer patients , the researchers found that by using immunotherapy to target the FAP molecule expressed by fibroblasts, this tissue's ability to enter immune cells may be reversed. Dr. Alexandre Calon said that when the FAP-IL2v molecule was added to reconstituted tumors in vitro containing the microenvironment resistant to this therapy, the potency of trastuzumab was restored upon contact with immune cells; it should be noted that , the researchers developed a model that uses human cells and is equally applicable to other types of tumors.
Original: doi:10.1038/s41467-022-32782-3
[6] Blood: Harnessing T cells expressing the ADR receptor holds promise for preventing graft-versus-host disease and cancer recurrence after allogeneic hematopoietic stem cell transplantation
2022-10-20 reported that in a new study, researchers from Baylor College of Medicine and Boston Children's Hospital and other research institutions in the United States genetically modified immune cells called T cells to control the blood cells usually used in allogeneic hematopoietic stem cell transplantation. There are two major life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment for leukemia: graft-vs-host disease (GvHD) and cancer recurrence. Their findings in animal models support further research to determine the feasibility of using this approach to reduce mortality and improve patient outcomes. Related research results were recently published in the journal Blood, titled "Engineering T cells to suppress acute GvHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation".
"In general, allo-HSCT transplantation is used to treat patients with aggressive disease who have not responded well to conventional treatments, and it has the potential to cure several types of blood cancer."
Original: doi:10.1182/blood.2022016052.
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【7】Science sub-journal: New research shows that CAR-T cells are expected to be used to treat fungal infections
2022-10-20 reported that in a new study, researchers from research institutions such as the University of Würzburg and the University of Munich in Germany developed a method to improve the CAR-T cell engineering process, according to which they Constructed CAR-T cells that can help fight fungal infections in the lungs. The relevant research results were published in the journal Science Translational Medicine on September 28, 2022. The title of the paper is "CAR T cells targeting Aspergillus fumigatus are effective at treating invasive pulmonary aspergillosis in preclinical models". In this paper, they describe improvements to the CAR-T cell engineering process.
The authors first tested their newly engineered CAR-T cells in petri dishes and found that they could recognize multiple strains of A. fumigatus. They also found that their CAR-T cells were able to kill the fungus by releasing perforin and granzyme B to hinder the growth of the fungus. They then tested their CAR-T cells on laboratory mice. They found that the CAR-T cells moved directly to the site of infection and, as they attached to the fungus, reduced the fungal population, which in turn helped the immune system eliminate the fungal infection. The authors suggest that T cell engineering approaches similar to those used to treat cancer cells could also be used in other applications, such as fighting fungal infections.
Original: doi:10.1126/scitranslmed.abh1209.