The Landscape of CAR-T Cell Clinical Trials against Solid Tumors—A Comprehensive Overview

Schaft, Niels

doi:10.3390/cancers12092567

Cited by 79 publications

(51 citation statements)

References 253 publications

(308 reference statements)

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“…Moreover, B7-H3.CAR-T cells’ efficacy in the treatment of pancreatic ductal adenocarcinoma in vitro and orthotopic as well as metastatic xenograft mouse models has been proven. Interestingly, 4-1BB co-stimulation supports lower PD-1 expression in generated T cells, and more antitumor activity when we want to target PD-L1 constitutively expressed tumor cells [ 80 , 81 ].…”

Section: Car T Cell Therapy In Solid Tumors: Recent Advancesmentioning

confidence: 99%

“…Colorectal NKG2D [54], EP-CAM [55], HER2 [56], GUCY2C [57], TAG-72 [58], CD46 [58] Liver CEA [59], Glypican3 [60], AFP [61] Gastric Mesothelin [62], ANTXR1 [63], MUC3A [63], Trop2 [64], Claudin18.2 [66], NKG2D [28], HER2 [65,66], FR-α [67] Pancreatic MUC1 [68], Mesothelin [69], αvβ6 [70], CEA [71], PSCA [71], FAP [71], CD47 [72], HER2 [73], NKG2D [74] Renal CAIX [75] Melanoma GD2 [76], GSPG4 [77], Glypican3 [78], HER2 [79] Cervix αvβ6 [80], L1-CAM [81] Neuroblastoma GD2 [82,83], CD56 [84], Glypican 2 [85], CD171 [86] Glioblastoma EGFRvIII [87], HER2 [88], B7-H3 [89], NKG2D [90], CAIX [91], αvβ3, IL13Rα2 [92] Ovarian Mesothelin [62,93], αvβ6…”

Section: Cancer Antigenmentioning

confidence: 99%

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CAR T cells in solid tumors: challenges and opportunities

et al. 2021

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Background CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

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Section: Car T Cell Therapy In Solid Tumors: Recent Advancesmentioning

confidence: 99%

Section: Cancer Antigenmentioning

confidence: 99%

CAR T cells in solid tumors: challenges and opportunities

et al. 2021

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“…Many clinical trials had focused on CAR-T therapy in hematological malignancies, and certain advances were made. However, solid tumors are less susceptible to this kind of therapy because of the lack of adequate cancer-specific antigens that can be targeted by CAR-T cells[ 154 ]. It has been shown that the density of target antigen may be a crucial factor for successful recognition and killing by CAR-T cells[ 16 ].…”

Section: B7-h3 As a Potential Therapeutic Target In Gastrointestinal Tumorsmentioning

confidence: 99%

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors

Rasic¹,

Jovanović-Tucović²,

Jeremic³

et al. 2021

WJGO

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The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches. Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3 (B7-H3) among the most common cancers of the GIT, including CRC, GC, and EC, whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal. This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms, and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways, such as Janus kinase 2/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB. B7-H3 exerts an important role in progression, metastasis and resistance to anticancer therapy in these tumors. In addition, the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response. Accordingly, it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response, impaired tumor progression, invasion, angiogenesis, and metastasis and decreased resistance to anticancer therapy. Finally, the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis. In this review, we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

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“…In recent years, immune checkpoint inhibitor (ICI) antibody therapy and chimeric antigen receptor T (CAR-T) cell therapies have been attracting attention as new immunotherapies for human cancers, with several approved molecules and indicators and thousands of clinical trials being conducted worldwide [83,84]. These could also hold potential for treating dogs, but in practice, canine cancer biology is less progressed, compared to human medicine, although research progress is continuously being made.…”

Section: Next Generations Of Immunotherapy In Dogsmentioning

confidence: 99%

Spontaneously occurring canine cancer as a relevant animal model for developing novel treatments for human cancers

Mizuno

2021

Translational and Regulatory Sciences

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The most common cause of death among adult or older dogs is malignancy. Dogs spontaneously develop malignant tumors with age, and the incidence of malignant tumors in dogs is higher than that in humans. Basic research on treatment of tumors is generally conducted using syngeneic or immunodeficient mice, which have some shortcomings as a model for human tumors that develop over a long period of time, while interacting with the host immune system. On the other hand, naturally occurring canine tumors develop under immunocompetent conditions and may be suitable for preclinical studies, especially for the development of therapies that affect host immunity. In this review, some of the canine tumors and immunotherapies that have been implemented thus far will be discussed, with the intent of helping establish cancer treatment research, using dogs with naturally occurring tumors, for translational studies in humans.

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The Landscape of CAR-T Cell Clinical Trials against Solid Tumors—A Comprehensive Overview

Cited by 79 publications

References 253 publications

CAR T cells in solid tumors: challenges and opportunities

CAR T cells in solid tumors: challenges and opportunities

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors

Spontaneously occurring canine cancer as a relevant animal model for developing novel treatments for human cancers

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