Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Kozani, Pouya Safarzadeh; Kozani, Pooria Safarzadeh; Najafabadi, Milad Ahmadi; Yousefi, Fatemeh; Mirarefin, Seyed Mohamad Javad; Rahbarizadeh, Fatemeh

doi:10.3389/fimmu.2022.795164

Cited by 48 publications

(45 citation statements)

References 195 publications

(338 reference statements)

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“…The list of the FDA-approved CAR-T products has been summarized in Table 1. However, patients with several hematologic malignancies, including T-cell neoplasms, as well as solid tumor patients have not yet benefited from the anticancer capability of this unique type of therapy (68)(69)(70). There are various limitations attributed to the inability of CAR-Ts to mediate tumor rejection and disease remission in solid tumors.…”

Section: Car-t Therapy Challenges In Solid Tumorsmentioning

confidence: 99%

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil

et al. 2022

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Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body’s immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.

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Section: Car-t Therapy Challenges In Solid Tumorsmentioning

confidence: 99%

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil

et al. 2022

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“…Currently, there are several ongoing clinical trials utilizing CAR-T cell therapy for solid tumors including glioblastoma [ 19 ], lung cancer [ 20 ], liver cancer [ 21 ], gastric cancer [ 22 ], renal cancer [ 23 ], prostate cancer [ 24 ], osteosarcoma, peritoneal carcinomatosis, pleural cancer, central nervous system tumors and neuroblastoma [ 25 ]. This immunotherapeutic approach generated promising clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

et al. 2023

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In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This approach consists of genetically engineered immune cells expressing a surface receptor, called CAR, that specifically targets antigens expressed on the surface of tumor cells. In hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T cell therapy has shown efficacy in treating chemotherapy refractory patients. However, the value of this therapy remains inconclusive in the context of solid tumors and is restrained by several obstacles including limited tumor trafficking and infiltration, the presence of an immunosuppressive tumor microenvironment, as well as adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) and CAR-macrophages (CAR-M) were introduced as a complement/alternative to CAR-T cell therapy for solid tumors. CAR-NK cells could be a favorable substitute for CAR-T cells since they do not require HLA compatibility and have limited toxicity. Additionally, CAR-NK cells might be generated in large scale from several sources which would suggest them as promising off-the-shelf product. CAR-M immunotherapy with its capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration, is currently being investigated. Here, we discuss the emerging role of CAR-T, CAR-NK, and CAR-M cells in solid tumors. We also highlight the advantages and drawbacks of CAR-NK and CAR-M cells compared to CAR-T cells. Finally, we suggest prospective solutions such as potential combination therapies to enhance the efficacy of CAR-cells immunotherapy.

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“…Furthermore, 3rd CARs that combined both CD28 and 4-1BB give the T cell stronger activation signals (16,17). The FDA has approved six 2 nd CAR T-cell therapies since 2017 as the result of positive clinical cases for anti-blood cancer treatment including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), follicular lymphoma, mantle cell lymphoma (MCL) and multiple myeloma (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Enhancing CAR T-cell therapies against solid tumors: Mechanisms and reversion of resistance

Qin

2022

Front. Immunol.

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Chimeric antigen receptor (CAR) T-cell therapy, belonging to adoptive immune cells therapy, utilizes engineered immunoreceptors to enhance tumor-specific killing. By now new generations of CAR T-cell therapies dramatically promote the effectiveness and robustness in leukemia cases. However, only a few CAR T-cell therapies gain FDA approval till now, which are applied to hematologic cancers. Targeting solid tumors through CAR T-cell therapies still faces many problems, such as tumor heterogeneity, antigen loss, infiltration inability and immunosuppressive micro-environment. Recent advances provide new insights about the mechanisms of CAR T-cell therapy resistance and give rise to potential reversal therapies. In this review, we mainly introduce existing barriers when treating solid tumors with CAR T-cells and discuss the methods to overcome these challenges.

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Recent Advances in Solid Tumor CAR-T Cell Therapy: Driving Tumor Cells From Hero to Zero?

Cited by 48 publications

References 195 publications

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil

CAR-T cell therapy in triple-negative breast cancer: Hunting the invisible devil

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

Enhancing CAR T-cell therapies against solid tumors: Mechanisms and reversion of resistance

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