Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures

Majumder, Avisek

doi:10.3390/cancers16010039

Cited by 7 publications

(3 citation statements)

References 213 publications

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“…ICANS is a common adverse event after CAR T-cell therapy and may manifest, e.g., as encephalopathy, aphasia, lethargy, disorientation, agitation, or cerebral edema [148,151,158,166]. These neurologic symptoms may occur simultaneously or after CRS [148,167].…”

Section: Immune Effector Cell-associated Neurotoxicity Syndrome (Icans)mentioning

confidence: 99%

“…Besides physical barriers, hypoxia and alterations in the energy metabolism of tumor cells lead to an uncomfortable area that limits the survival and function of different immune cells because of a lack of nutrition and oxygen [169]. Additionally, tumor cells and the surrounding bystander cells (e.g., regulatory T-cells) actively inhibit immune cell function by secreting immunosuppressive cytokines, leading to anergy and the apoptosis of tumor-infiltrating lymphocytes and immune effector cells [76,80,166].…”

Section: Car T-cell Therapy In Solid Oncologymentioning

confidence: 99%

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Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations

Blüm,

Kayser

2024

Cancers

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Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more are being developed and investigated in clinical trials. The whole field of adoptive cell transfer has experienced an unbelievable development process, and we are now at the edge of a new era of immune therapies that will have its impact beyond hematologic malignancies. Areas of interest are, e.g., solid oncology, autoimmune diseases, infectious diseases, and others. Although much has been achieved so far, there is still a huge effort needed to overcome significant challenges and difficulties. We are witnessing a rapid expansion of knowledge, induced by new biomedical technologies and CAR designs. The era of CAR T-cell therapy has just begun, and new products will widen the therapeutic landscape in the future. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges.

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Section: Immune Effector Cell-associated Neurotoxicity Syndrome (Icans)mentioning

confidence: 99%

Section: Car T-cell Therapy In Solid Oncologymentioning

confidence: 99%

Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations

Blüm,

Kayser

2024

Cancers

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“…Various studies have shown that IL-6 and its soluble receptors are increased in UC patients and play an essential role in the pathogenesis of UC and colorectal cancers related to UC [ 176 ]. T cells, part of adaptive immunity, also participate in UC [ 177 ]. T cells differentiate into Th17 cells when they encounter inflammatory mediators in the GI.…”

Section: Association Of the Microbiome With The Modulation Of Immunol...mentioning

confidence: 99%

How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer

Majumder,

Bano

2024

Biomolecules

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Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host’s epigenetic reprogramming. Additionally, overproduction of H2S from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome’s function and alters the host’s physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.

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Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches

Ramalingam,

Premkumar,

Sundararajan

et al. 2024

Discov Onc

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Mutant KRAS promotes the proliferation, metastasis, and aggressiveness of various cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal adenocarcinoma (CRC) respectively. Mutant KRAS therapeutics are limited, while Sotorasib and Adagrasib were the only FDA-approved drugs for the treatment of KRASG12C mutated NSCLC. Chimeric antigen receptor (CAR) T-cell therapy has been emerged as an effective strategy against hematological malignancies and being extended towards solid cancers including PDAC. mesothelin (MSLN) and Carcinoembryonic Antigen (CEA) were reported to be highly overexpressed in KRAS-mutated PDAC. Meanwhile, in clinical trials, several CAR T-cell therapy studies are mainly focused towards these two cancer antigens in PDAC, however, the dual targeting of these two neoantigens is not reported. In the present study, we have designed and developed a novel dual-targeting CAR protein by employing various bioinformatics approaches such as functional analysis (antigenicity, allergenicity, antigen binding sites & signalling cascades), qualitative analysis (physicochemical, prediction, refinement & validation of 2D and 3D structures), molecular docking, and in silico cloning. Our results revealed that the designed CAR protein specifically binds with both MSLN & CEA with significant binding affinities, and was predicted to be stable & non-allergenic. Additionally, the protein–protein interaction network reveals the T-cell mediated antitumor responses of each domain in the designed CAR. Conclusively, we have designed and developed a dual targeting (MSLN & CEA) CAR protein towards KRAS-mutated PDAC using computational approaches. Alongside, we further recommend to engineer this designed CAR in T-cells and evaluating their therapeutic efficiency in in vitro and in vivo studies in the near future.

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Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures

Cited by 7 publications

References 213 publications

Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations

Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations

How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer

Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches

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