CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy

Tian, Yonggui; Wen, Chunli; Zhang, Zhen; Liu, Yanfen; Li, Feng; Zhao, Qitai; Yao, Chang; Ni, Kaiyuan; Yang, Shengli; Zhang, Yi

doi:10.1007/s00262-022-03193-6

Cited by 25 publications

(11 citation statements)

References 55 publications

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“…An enhanced expression of CXCL9 in cancer tissue than healthy tissue was also observed in the second Chinese study, where CXCL9 expression levels were associated with tumor stage and survival ( 39 ). Importantly, CXCL9 may also recruit T-cells to the TME and exerts antitumor activity ( 40 ). The chemokine, CCL23 has been found as a cytokine with both, pro- and anti-cancer properties.…”

Section: Discussionmentioning

confidence: 99%

Plasma protein changes reflect colorectal cancer development and associated inflammation

Urbiola-Salvador,

Jabłońska,

Miroszewska

et al. 2023

Front. Oncol.

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IntroductionColorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed.MethodsTo identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few μL of plasma sample.ResultsAmong the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC.DiscussionFurther study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.

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Section: Discussionmentioning

confidence: 99%

Plasma protein changes reflect colorectal cancer development and associated inflammation

Urbiola-Salvador,

Jabłońska,

Miroszewska

et al. 2023

Front. Oncol.

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“…In addition, engineering cytokine receptors represented by orthogonal IL-2 has been found to enhance T cell antitumor function while attenuating the side effects caused by cytokine pleiotropy [96][97][98]. And T cells engineered to secrete additional cytokines (IL-7/12/15/18/23 and Flt3L) or chemokines (CXCL9/10/11 and CCL19/21) also show enhancement of activity and function [99][100][101][102][103][104][105][106][107][108][109]. These strategies improve the function of autologous tumor-reactive T cells, promote their phenotype switching, and, meanwhile, recruit other immune cells (such as NK cells and DCs) to exert antitumor effects.…”

Section: Feasible Engineering Strategies For Nrt Cellsmentioning

confidence: 99%

Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches

et al. 2023

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Neoantigens generated by non-synonymous mutations of tumor genes can induce activation of neoantigen-reactive T (NRT) cells which have the ability to resist the growth of tumors expressing specific neoantigens. Immunotherapy based on NRT cells has made preeminent achievements in melanoma and other solid tumors. The process of manufacturing NRT cells includes identification of neoantigens, preparation of neoantigen expression vectors or peptides, induction and activation of NRT cells, and analysis of functions and phenotypes. Numerous improvement strategies have been proposed to enhance the potency of NRT cells by engineering TCR, promoting infiltration of T cells and overcoming immunosuppressive factors in the tumor microenvironment. In this review, we outline the improvement of the preparation and the function assessment of NRT cells, and discuss the current status of clinical trials related to NRT cell immunotherapy.

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“…However, there is controversy about the optimal chemokine receptor used to improve CAR-T cell trafficking (190). Furthermore, many chemokines are used as target antigens for CAR-T cells in solid tumor treatment (172,(191)(192)(193).…”

Section: Improving Traffickingmentioning

confidence: 99%

Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities

Chen

Niu

et al. 2022

Front. Immunol.

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Different from surgery, chemical therapy, radio-therapy and target therapy, Chimeric antigen receptor-modified T (CAR-T) cells, a novel adoptive immunotherapy strategy, have been used successfully against both hematological tumors and solid tumors. Although several problems have reduced engineered CAR-T cell therapeutic outcomes in clinical trials for the treatment of thoracic malignancies, including the lack of specific antigens, an immunosuppressive tumor microenvironment, a low level of CAR-T cell infiltration into tumor tissues, off-target toxicity, and other safety issues, CAR-T cell treatment is still full of bright future. In this review, we outline the basic structure and characteristics of CAR-T cells among different period, summarize the common tumor-associated antigens in clinical trials of CAR-T cell therapy for thoracic malignancies, and point out the current challenges and new strategies, aiming to provide new ideas and approaches for preclinical experiments and clinical trials of CAR-T cell therapy for thoracic malignancies.

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CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy

Cited by 25 publications

References 55 publications

Plasma protein changes reflect colorectal cancer development and associated inflammation

Plasma protein changes reflect colorectal cancer development and associated inflammation

Adoptive neoantigen-reactive T cell therapy: improvement strategies and current clinical researches

Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities

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