Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors

Zhang, Binglan; Qin, Diyuan; Mo, Zeming; Li, Yang; Wei, Wei; Wang, Yongsheng; Wang, Wei; Wei, Yuquan

doi:10.1007/s11427-016-5027-4

Cited by 83 publications

(66 citation statements)

References 89 publications

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“…Once they accumulate in the vicinity, they must efficiently infiltrate into the tumor. After migrating into the solid tumor lesion, CAR-T cells must overcome hostile immunosuppressive elements to elicit specific cytotoxicity 192 , as shown in Fig. 1.…”

Section: Use Of Genetically Engineered T Cells For Treating Solid Tumorsmentioning

confidence: 99%

Genetically engineered T cells for cancer immunotherapy

Zhou

et al. 2019

Sig Transduct Target Ther

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185

102

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T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers.

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Section: Use Of Genetically Engineered T Cells For Treating Solid Tumorsmentioning

confidence: 99%

Genetically engineered T cells for cancer immunotherapy

Zhou

et al. 2019

Sig Transduct Target Ther

Self Cite

185

102

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“…Clinical trials on the applicability of CAR-T therapy for the treatment of HCC are summarized in Table 2. Antigens involving GPC3, ErB2, GD2, EGFR, PSMA, and MUC1 are targeted in CAR-T therapy for solid tumors [47,49,50]. As is the case in hematologic malignancies, the suitable target for solid tumors must be selected to avoid side effects resulting from on-target, off tumor toxicity [32].…”

Section: Car-t Immunotherapy a Special Kind Of Actmentioning

confidence: 99%

Adoptive cell transfer therapy for hepatocellular carcinoma

Zhang

et al. 2019

Front. Med.

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CART immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CART could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CART technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.

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“…During the past decade, CARs have demonstrated remarkable effects on patients with hematological tumors [ 75 , 76 ]. Using them to target solid tumors, however, is challenging, probably because of features in their histopathological structure and their difficulty in T-cell trafficking and T-cell infiltration into tumor sites [ 77 ]. Solid tumors have special histopathological features, including poor integrity of issue structure, a high concentration of blood vessels, and extensive vascular leakage.…”

Section: Rationality Of Car-t Cells Therapy In Ocmentioning

confidence: 99%

CAR-T cell therapy in ovarian cancer: from the bench to the bedside

et al. 2017

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Ovarian cancer (OC) is the most lethal gynecological malignancy and is responsible for most gynecological cancer deaths. Apart from conventional surgery, chemotherapy, and radiotherapy, chimeric antigen receptor-modified T (CAR-T) cells as a representative of adoptive cellular immunotherapy have received considerable attention in the research field of cancer treatment. CARs combine antigen specificity and T-cell-activating properties in a single fusion molecule. Several preclinical experiments and clinical trials have confirmed that adoptive cell immunotherapy using typical CAR-engineered T cells for OC is a promising treatment approach with striking clinical efficacy; moreover, the emerging CAR-Ts targeting various antigens also exert great potential. However, such therapies have side effects and toxicities, such as cytokine-associated and “on-target, off-tumor” toxicities. In this review, we systematically detail and highlight the present knowledge of CAR-Ts including the constructions, vectors, clinical applications, development challenges, and solutions of CAR-T-cell therapy for OC. We hope to provide new insight into OC treatment for the future.

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Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors

Cited by 83 publications

References 89 publications

Genetically engineered T cells for cancer immunotherapy

Genetically engineered T cells for cancer immunotherapy

Adoptive cell transfer therapy for hepatocellular carcinoma

CAR-T cell therapy in ovarian cancer: from the bench to the bedside

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