CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma

Park, Yuk Pheel; Jin, Linchun; Bennett, Katie B.; Wang, Dunrui; Fredenburg, Kristianna M.; Tseng, Jennifer; Chang, Lung‐Ji; Huang, Jianping; Chan, Edward K. L.

doi:10.1016/j.oraloncology.2018.01.024

Cited by 45 publications

(35 citation statements)

References 22 publications

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“…Although numerous TAAs have been detected in HNSCC, the current literature on CAR‐T treatments report those targeting CD70 and human epidermal growth receptor factor 2 (Her2) . Therefore, it is important to broaden the HNSCC‐specific targets of CAR‐T cells.…”

Section: Discussionmentioning

confidence: 99%

MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

et al. 2019

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The modification of chimeric antigen receptor (CAR) endowing T cells with tumorspecific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR-T therapy. The purpose of our study was to find and verify the potentials of CAR-T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non-neoplastic tissues (ANNT). Next, we constructed a second-generation CAR and validated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth-generation CAR that secretes IL22. Finally, we verified the antitumor function of two different CAR-T cells in vitro and in vivo, respectively. CAR-MUC1-IL22 T cells were found to have a stronger and more effective cytotoxic function against MUC1 + HNSCC cells.Taken together, these results demonstrate the potential effectiveness of CAR-T in the treatment of patients with HNSCC and provide evidence-based of MUC1 + CAR-T therapy. K E Y W O R D SCAR-T, head and neck squamous cell carcinoma, IL22, MUC1 | 641 MEI Et al.

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Section: Discussionmentioning

confidence: 99%

MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

et al. 2019

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“…In recent years, synthetic chimeric antigen receptor (CAR)‐T cell therapy has encouraging therapeutic potential in HNSCCs and hematological cancers 128–130 . A previous study identified nine overexpressed genes on the surface of HNSCCs as potential targets for CAR‐T cell therapy, 128 but only a few targeted antigens have shown favorable results. Preclinical and clinical data on HER2‐specific, CD70‐specific, and T4 (T1E28ζ/4αβ) CAR‐T cell therapy on HNSCCs demonstrate potent antitumor activity, but the risk of on‐target off‐tumor toxicity remains a challenge to overcome 128,129,131 .…”

Section: Current and Future Immunotherapies In Hnsccmentioning

confidence: 99%

“…A previous study identified nine overexpressed genes on the surface of HNSCCs as potential targets for CAR‐T cell therapy, 128 but only a few targeted antigens have shown favorable results. Preclinical and clinical data on HER2‐specific, CD70‐specific, and T4 (T1E28ζ/4αβ) CAR‐T cell therapy on HNSCCs demonstrate potent antitumor activity, but the risk of on‐target off‐tumor toxicity remains a challenge to overcome 128,129,131 . T4 + CAR T‐cells are retrovirally transduced to coexpress (a) T1E28ζ, a CAR coupling ErbB ligand derived from EGF and TGFα to a fused CD28/CD3ζ endodomain; and (b) 4αβ, a chimeric cytokine receptor containing the IL‐4Rα ectodomain coupled to the IL‐2Rβ endodomain 131 …”

Section: Current and Future Immunotherapies In Hnsccmentioning

confidence: 99%

Tumor immune microenvironment in head and neck cancers

Chen

Krinsky

Woolaver

et al. 2020

Molecular Carcinogenesis

110

114

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Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide.Ninety percent of head and neck cancers are squamous cell carcinomas (HNSCCs).The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.

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“…The aberrant expression of CD70 has been detected on hematological malignancies and also on some solid tumors, such as osteosarcoma, renal cell carcinoma, thymic carcinoma, nasopharyngeal carcinoma and glioblastoma 10 - 14 . Several reports have also provided the evidence suggesting the therapeutic potential of CD70 targeted CAR-T cell 15 , 16 .…”

Section: Introductionmentioning

confidence: 99%

Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors

et al. 2020

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Purpose: Given that heterogeneous expression and variants of antigens on solid tumors are responsible for relapse after chimeric antigen receptor (CAR)-T cell therapy, we hypothesized that combinatorial targeting two tumor-associated antigens would lessen this problem and enhance the antitumor activity of T cells. Methods: The co-expression level of CD70 and B7-H3 was analyzed in multiple tumor tissue samples. Further, two putative antigens were identified in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis database. Two CD70 targeted CARs with different antigen binding domain, truncated CD27 and CD70 specific single-chain antibody fragment (scFv), were designed to screen a more suitable target-antigen binding moiety. Accordingly, we designed a bivalent tandem CAR (TanCAR) and further assessed the anti-tumor efficacy of TanCAR-T cells in vitro and in vivo . Results: Our results indicated that co-expression of CD70 and B7-H3 was observed on multiple tumor types including kidney, breast, esophageal, liver, colon cancer, glioma as well as melanoma. The CD70 targeted CAR-T cells with binding moiety of CD70 specific scFv exhibit a higher affinity and antitumor effect against CD70 + tumor cells. TanCAR-T cells induced enhanced ability of cytolysis and cytokine release over unispecific CAR-T cells when encountering tumor cells expressing two target-antigens. Further, low doses of TanCAR-T cells could also effectively control the lung cancer and melanoma xenografts and improved overall survival of the treated animals. Conclusion: TanCAR-T cells targeting CD70 and B7-H3 exhibit enhanced antitumor functionality and improve the problem of antigenic heterogeneity and variant in the treatment against solid tumor and melanoma.

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CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma

Abstract: CD70-specific CAR-T cells specifically recognized and efficiently eliminated CD70-positive HNSCC cells. This study provides the basis for further investigation into CD70 and other CAR-T targets.

Cited by 45 publications

References 22 publications

MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

MUC1 as a target for CAR‐T therapy in head and neck squamous cell carinoma

Tumor immune microenvironment in head and neck cancers

Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors

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