Journal Articles

Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma

PURPOSE: The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide treatment choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitor (ICI) therapy in the real world is not well known. METHODS: Using a deidentified nationwide (US-based) melanoma clinicogenomic database, we identified a real-world cohort of patients with metastatic melanoma (N = 497) who received first-line monotherapy anti-PD-1 (n = 240) or dual anti-PD-1 and anti-CTLA-4 ICI (n = 257) and had a tissue-based comprehensive genomic profiling test TMB score. RESULTS: TMB-high (TMB-H; ³10 mutations per megabase [muts/Mb], n = 352, 71%) was independently predictive of superior real-world progression-free survival and overall survival versus TMB-low (<10 mut/Mb, n = 145, 29%) in both mono ICI (hazard ratio [HR], 0.45 [95% CI, 0.32 to 0.63]; P < .001; HR, 0.61 [95% CI, 0.41 to 0.90]; P = .01, respectively) and dual ICI (HR, 0.67 [95% CI, 0.49 to 0.90]; P = .009; HR, 0.61 [95% CI, 0.42 to 0.88]; P = .007, respectively) patients. Dual ICI offered no significant advantage in BRAFwt patients and unexpectedly demonstrated greatest benefit in the TMB 10-19 mut/Mb group, identifying a TMB-very high (³20 mut/Mb, n = 247, 50%) BRAFmut patient subgroup for whom mono ICI may be preferable. CONCLUSION: TMB-H predicts superior outcomes on ICI while coassessment of BRAF status and TMB may inform first-line regimen choice.

Author Info: (1) Department of Medicine, School of Translational Medicine, Monash University, Melbourne, VIC, Australia. Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia

Author Info: (1) Department of Medicine, School of Translational Medicine, Monash University, Melbourne, VIC, Australia. Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia. (2) Foundation Medicine, Cambridge, MA. (3) Foundation Medicine, Cambridge, MA. (4) Foundation Medicine, Cambridge, MA. (5) Foundation Medicine, Cambridge, MA. (6) Foundation Medicine, Cambridge, MA. (7) Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia. (8) Department of Medicine, School of Translational Medicine, Monash University, Melbourne, VIC, Australia. Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia. (9) Department of Medicine, School of Translational Medicine, Monash University, Melbourne, VIC, Australia. Department of Medical Oncology, Alfred Health, Melbourne, VIC, Australia. (10) Foundation Medicine, Cambridge, MA. (11) Foundation Medicine, Cambridge, MA.

Current Approaches and Novel New Agents in the Treatment of Chronic Lymphocytic Leukemia

The treatment of CLL has evolved from traditional chemoimmunotherapy (CIT) to an increasing number of targeted and biologic approaches. Randomized trials have demonstrated superiority of covalent bruton tyrosine kinase inhibitors (cBTKis) over CIT, and second-generation compounds such as acalabrutinib and zanubrutinib appear to have a more favorable efficacy/safety profile than ibrutinib. The noncovalent BTKi, pirtobrutinib, has shown impressive activity after failure of the cBTKis and is quite tolerable. The Bcl-2 inhibitor venetoclax plus a CD20, generally obinutuzumab, provides a high level of efficacy as initial treatment or after failure on a cBTKi, with many patients achieving a state of undetectable minimal residual disease. Promising novel approaches include BTK degraders, bispecific antibodies, and chimeric antigen receptor T-cell (CAR-T)-cell therapy. What is clear is that CIT is archaic, and current and future targeted approaches will continue to improve the outcome for patients with chronic lymphocytic leukemia.

Author Info: (1) Center for Cancer and Blood Disorders, Bethesda, MD. (2) Willamette Valley Cancer Institute, Medical Director of Hematology Research: Sara Cannon, Eugene, OR.

Author Info: (1) Center for Cancer and Blood Disorders, Bethesda, MD. (2) Willamette Valley Cancer Institute, Medical Director of Hematology Research: Sara Cannon, Eugene, OR.

Efficacy of immunotherapy in ARID1A-mutant solid tumors: a single-center retrospective study

BACKGROUND: Immune checkpoint inhibitors (ICIs), especially those targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have introduced a new treatment landscape for many types of tumors. However, they only achieve a limited therapeutic response. Hence, identifying patients who may benefit from ICIs is currently a challenge. METHODS: 47 tumor patients harboring ARID1A mutations were retrospectively studied. The genomic profiling data through next-generation sequencing (NGS) and relevant clinical information were collected and analyzed. Additionally, bioinformatics analysis of the expression of immune checkpoints and immune cell infiltration levels was conducted in ARID1A-mutant gastric cancer (GC). RESULTS: ARID1A mutations frequently co-occur with mutations in DNA damage repair (DDR)-associated genes. Among the 35 ARID1A-mutant patients who received immunotherapy, 27 were evaluable., with the objective response rate (ORR) was 48.15% (13/27), and the disease control rate (DCR) was 92.59% (25/27). Moreover, survival assays revealed that ARID1A-mutant patients had longer median overall survival (mOS) after immunotherapy. In ARID1A-mutated GC patients, receiving ICIs treatment indicated longer progressive-free survival (PFS). Additionally, the incidence of microsatellite instability-high (MSI-H), high tumor mutation burden (TMB-H) and Epstein_Barr virus (EBV) infection was elevated. Bioinformatic analysis showed significant enrichment of immune response and T cell activation pathway within differentially expressed genes in ARID1A-mutant GC group. Finally, ARID1A mutations status was considered to be highly correlated with the level of tumor infiltrating lymphocytes (TILs) and high expression of immune checkpoints. CONCLUSIONS: Patients with tumors harboring ARID1A mutations may achieve better clinical outcomes from immunotherapy, especially in GC. ARID1A mutations can lead to genomic instability and reshape the tumor immune microenvironment (TIME), which can be used as a biomarker for immunotherapy.

Author Info: (1) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (2) Department of Medical Oncology, National Cancer

Author Info: (1) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (2) Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. (3) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (4) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (5) Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. (6) Precision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. (7) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (8) Medical College of Qingdao University, No.308 Ningxia Road, Qingdao, 266000, Shandong, China. (9) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. (10) Department of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China. houheleihhl@163.com.

Machine learning-based identification of a cell death-related signature associated with prognosis and immune infiltration in glioma

Accumulating evidence suggests that a wide variety of cell deaths are deeply involved in cancer immunity. However, their roles in glioma have not been explored. We employed a logistic regression model with the shrinkage regularization operator (LASSO) Cox combined with seven machine learning algorithms to analyse the patterns of cell death (including cuproptosis, ferroptosis, pyroptosis, apoptosis and necrosis) in The Cancer Genome Atlas (TCGA) cohort. The performance of the nomogram was assessed through the use of receiver operating characteristic (ROC) curves and calibration curves. Cell-type identification was estimated by using the cell-type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and single sample gene set enrichment analysis methods. Hub genes associated with the prognostic model were screened through machine learning techniques. The expression pattern and clinical significance of MYD88 were investigated via immunohistochemistry (IHC). The cell death score represents an independent prognostic factor for poor outcomes in glioma patients and has a distinctly superior accuracy to that of 10 published signatures. The nomogram performed well in predicting outcomes according to time-dependent ROC and calibration plots. In addition, a high-risk score was significantly related to high expression of immune checkpoint molecules and dense infiltration of protumor cells, these findings were associated with a cell death-based prognostic model. Upregulated MYD88 expression was associated with malignant phenotypes and undesirable prognoses according to the IHC. Furthermore, high MYD88 expression was associated with poor clinical outcomes and was positively related to CD163, PD-L1 and vimentin expression in the in-horse cohort. The cell death score provides a precise stratification and immune status for glioma. MYD88 was found to be an outstanding representative that might play an important role in glioma.

Author Info: (1) The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. (2) The National Key Clinical Specialty, Depa

Author Info: (1) The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. (2) The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China. (3) Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China. (4) Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China. (5) Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China. (6) NHC Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China. (7) The National Key Clinical Specialty, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Single-cell and Bulk Transcriptomic Analyses Reveal a Stemness and Circadian Rhythm Disturbance-related Signature Predicting Clinical Outcome and Immunotherapy Response in Hepatocellular Carcinoma

AIMS: Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response. BACKGROUND: Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells. OBJECTIVE: Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC. METHODS: The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature. RESULTS: A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts. CONCLUSIONS: In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.

Author Info: (1) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (2) College of Bioinformatics Science and Technology, Harbin Medical University, Har

Author Info: (1) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (2) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (3) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (4) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (5) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (6) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (7) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. (8) College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Comparison of seven CD19 CAR designs in engineering NK cells for enhancing anti-tumour activity

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is emerging as a promising cancer treatment, with notable safety and source diversity benefits over CAR-T cells. This study focused on optimizing CAR constructs for NK cells to maximize their therapeutic potential. We designed seven CD19 CAR constructs and expressed them in NK cells using a retroviral system, assessing their tumour-killing efficacy and persistence. Results showed all constructs enhanced tumour-killing and prolonged survival in tumour-bearing mice. In particular, CAR1 (CD8 TMD-CD3_ SD)-NK cells showed superior efficacy in treating tumour-bearing animals and exhibited enhanced persistence when combined with OX40 co-stimulatory domain. Of note, CAR1-NK cells were most effective at lower effector-to-target ratios, while CAR4 (CD8 TMD-OX40 CD- Fc_RI_ SD) compromised NK cell expansion ability. Superior survival rates were noted in mice treated with CAR1-, CAR2 (CD8 TMD- Fc_RI_ SD)-, CAR3 (CD8 TMD-OX40 CD- CD3_ SD)- and CAR4-NK cells over those treated with CAR5 (CD28 TMD- Fc_RI_ SD)-, CAR6 (CD8 TMD-4-1BB CD-CD3_ 1-ITAM SD)- and CAR7 (CD8 TMD-OX40 CD-CD3_ 1-ITAM SD)-NK cells, with CAR5-NK cells showing the weakest anti-tumour activity. Increased expression of exhaustion markers, especially in CAR7-NK cells, suggests that combining CAR-NK cells with immune checkpoint inhibitors might improve anti-tumour outcomes. These findings provide crucial insights for developing CAR-NK cell products for clinical applications.

Author Info: (1) Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Ce

Author Info: (1) Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. University of Chinese Academy of Sciences, Beijing, China. (2) Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. University of Chinese Academy of Sciences, Beijing, China. (3) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. University of Chinese Academy of Sciences, Beijing, China. (4) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (5) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (6) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (7) Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. (8) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. University of Chinese Academy of Sciences, Beijing, China. (9) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (10) Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. (11) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. (12) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (13) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. (14) Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. (15) State Key Laboratory of Experimental Hematology & National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. Center for Stem Cell Medicine & Department of Stem Cell and Regenerative Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China. (16) Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, Hangzhou, China. (17) Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. (18) State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. University of Chinese Academy of Sciences, Beijing, China.

Factor of time in dendritic cell (DC) maturation: short-term activation of DCs significantly improves type 1 cytokine production and T cell responses

Dendritic cells (DCs) have been intensively studied in correlation to tumor immunology and for the development DC-based cancer vaccines. Here, we present the significance of the temporal aspect of DC maturation for the most essential subsequent timepoint, namely at interaction with responding T cells or after CD40-Ligand restimulation. Mostly, DC maturation is still being achieved by activation processes which lasts 24 h to 48 h. We hypothesized this amount of time is excessive from a biological standpoint and could be the underlying cause for functional exhaustion. Indeed, shorter maturation periods resulted in extensive capacity of monocyte-derived DCs to produce inflammatory cytokines after re-stimulation with CD40-Ligand. This effect was most evident for the primary type 1 polarizing cytokine, IL-12p70. This capacity reached peak at 6 h and dropped sharply with longer exposure to initial maturation stimuli (up to 48 h). The 6 h maturation protocol reflected superiority in subsequent functionality tests. Namely, DCs displayed twice the allostimulatory capacity of 24 h- and 48 h-matured DCs. Similarly, type 1 T cell response measured by IFN-_ production was 3-fold higher when CD4(+) T cells had been stimulated with shortly matured DC and over 8-fold greater in case of CD8(+) T cells, compared to longer matured DCs. The extent of melanoma-specific CD8(+) cytotoxic T cell induction was also greater in case of 6 h DC maturation. The major limitation of the study is that it lacks in vivo evidence, which we aim to examine in the future. Our findings show an unexpectedly significant impact of temporal exposure to activation signals for subsequent DC functionality, which we believe can be readily integrated into existing knowledge on in vitro/ex vivo DC manipulation for various uses. We also believe this has important implications for DC vaccine design for future clinical trials.

Author Info: (1) Slovenian Institute for Transfusion Medicine, _lajmerjeva 6, Ljubljana, 1000, Slovenia. Faculty of Medicine, University of Ljubljana, Korytkova ulica 2, Ljubljana, 1000, Sloven

Author Info: (1) Slovenian Institute for Transfusion Medicine, _lajmerjeva 6, Ljubljana, 1000, Slovenia. Faculty of Medicine, University of Ljubljana, Korytkova ulica 2, Ljubljana, 1000, Slovenia. (2) Slovenian Institute for Transfusion Medicine, _lajmerjeva 6, Ljubljana, 1000, Slovenia. (3) Slovenian Institute for Transfusion Medicine, _lajmerjeva 6, Ljubljana, 1000, Slovenia. urban.svajger@ztm.si. Faculty of Pharmacy, University of Ljubljana, A_ker_eva 7, Ljubljana, 1000, Slovenia. urban.svajger@ztm.si.

Engineered T Cell Receptor for Cancer Immunotherapy

Among therapeutic strategies in cancer immunotherapy, involving immune-modulating antibodies, cancer vaccine or adoptive T cell transfer, T cells has been attractive target due to their cytotoxicity toward tumor cells and tumor antigen-specific binding of receptors. Taking advantage of exclusive properties of T cells, chimeric antigen receptor (CAR)-T and T cell receptor (TCR)-T cells were generated by genetic edition of their receptors, which led an improvement in specificity and effectiveness of the T cell therapy. Adoptive cell transfer of CAR-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen (TAA), which is called TCR-T therapy. Here in, this review discusses anti-tumor T cell therapies with focus on engineered TCR-T cell therapy. We describe features of TCR-T cell therapy, and clinical application of TCR-T cell therapy to non-hematological malignancies.

Author Info: (1) College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea. (2) College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea.

Author Info: (1) College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea. (2) College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea.

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n_=_15) and a dose-expansion stage in four different cohorts (total n_=_83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5___10(8), six with 3.75___10(8) and three with 5.0___10(8) CAR T cells. Median follow-up was 32.4_months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4_months (95% CI: 3.7, 6.6) and 8.8_months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

Author Info: (1) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Early Dr

Author Info: (1) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. changsongqi@bjmu.edu.cn. (2) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. (3) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (4) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. (5) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (6) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. (7) Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (8) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (9) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. (10) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (11) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (12) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (13) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (14) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (15) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (16) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (17) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (18) Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. (19) CARsgen Therapeutics Co., Ltd., Shanghai, China. (20) CARsgen Therapeutics Co., Ltd., Shanghai, China. (21) CARsgen Therapeutics Co., Ltd., Shanghai, China. (22) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. oncogene@163.com. (23) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. zhangxiaotian@bjmu.edu.cn. (24) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China. shenlin@bjmu.edu.cn.

NHS England launches scheme to boost signups for personalised cancer vaccine trials

NO ABSTRACT

Author Info: (1) The BMJ.

Author Info: (1) The BMJ.

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