CD70: An emerging target in cancer immunotherapy

Jacobs, Julie; Deschoolmeester, Vanessa; Zwaenepoel, Karen; Rolfo, Christian; Silence, Karen; Rottey, Sylvie; Lardon, Filip; Smits, Evelien; Pauwels, Patrick

doi:10.1016/j.pharmthera.2015.07.007

Cited by 148 publications

(164 citation statements)

References 97 publications

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“…The CD70/CD27 pathway is currently an area of interest [58]. CD70 is implicated in tumour cell and regulatory T cell survival through interaction with its ligand CD27 [58].…”

Section: Pd-1 or Pd-l1 Blockade In Combination With Other Adaptive Immentioning

confidence: 99%

See 1 more Smart Citation

PD-1 and PD-L1 blockade in gastrointestinal malignancies

Lote

Cafferkey

Chau

2015

Cancer Treatment Reviews

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“…The CD70/CD27 pathway is currently an area of interest [58]. CD70 is implicated in tumour cell and regulatory T cell survival through interaction with its ligand CD27 [58].…”

Section: Pd-1 or Pd-l1 Blockade In Combination With Other Adaptive Immentioning

confidence: 99%

“…CD70 is implicated in tumour cell and regulatory T cell survival through interaction with its ligand CD27 [58]. Combining CD70-CD27 blockade with other immune checkpoint inhibitors might enhance anticancer immune responses [58]; Phase I trials are currently ongoing ( …”

Section: Pd-1 or Pd-l1 Blockade In Combination With Other Adaptive Immentioning

confidence: 99%

PD-1 and PD-L1 blockade in gastrointestinal malignancies

Lote

Cafferkey

Chau

2015

Cancer Treatment Reviews

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“…Studies on CD70 expression revealed the same restricted expression profile in both humans and mice (9, 10), with CD70 only found on a small percentage of activated T cells and antigen presenting cells in draining lymph nodes during viral infection (10). Interestingly, a number of human tumors can also express CD70 including solid cancers such as clear cell renal cancer (RCC), glioblastoma, and hematological malignancies (11-14). The mechanism of overexpression of CD70 on tumors remains unknown, but a recent study suggested the dysregulated pVHL/HIF pathway may be involved in RCC (15).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers

Wang

Hanada

et al. 2017

Clinical Cancer Research

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Purpose CD70 expression in normal tissues is restricted to activated lymphoid tissues. Targeting CD70 on CD70-expressing tumors could mediate “on-target, off-tumor” toxicity. This study was to evaluate the feasibility and safety of using anti-human CD70 CARs to treat cancer patients whose tumors express CD70. Experimental Design Seven anti-human CD70 CARs with binding moieties from human CD27 combined with CD3-zeta and different co-stimulatory domains from CD28 and/or 41BB were constructed. In vitro functionality of these receptors was compared and in vivo treatment efficacy was evaluated in a xenograft mouse model. A homologous, all murine anti-CD70 CAR model was also used to assess treatment-related toxicities. Results The CAR consisting of the extracellular binding portion of CD27 fused with 41BB and CD3-zeta (trCD27-41BB-zeta) conferred the highest IFN-γ production against CD70-expressing tumors in vitro, and NSG mice bearing established CD70-expressing human tumors could be cured by human lymphocytes transduced with this CAR. In the murine CD27-CD3-zeta CAR model, significant reduction of established tumors and prolonged survival were achieved using CAR-transduced splenocytes in a dose-dependent manner. Host pre-irradiation enhanced treatment efficacy but increased treatment-related toxicities such as transient weight loss and hematopoetic suppression. The treatment did not appear to block adaptive host immune responses. Conclusions Pre-clinical testing supports the safety and efficacy of a CD27-containing CAR targeting CD70-expressing tumors.

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“…Hitherto, there is no uniform reporting of CD70 IHC in malignancies in the literature. The use of different methods (formalin-fixed paraffin-embedded or frozen-section), different antibody clones and different thresholds for positivity make it impossible to compare these results [8]. Moreover, as demonstrated here, different cellular expression patterns of CD70 can be discerned, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…However, CD70 expression has been reported in a variety of human malignancies (e.g. lymphoma, leukemia, renal cell carcinoma and nasopharyngeal carcinoma) [8]. In this context, CD70 contributes to an immunosuppressive microenvironment by augmenting and/or attracting regulatory T cells, inducing T cell apoptosis and stimulating T cell exhaustion [9,10,11].…”

Section: Introductionmentioning

confidence: 99%

CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck

Meulenaere¹,

Vermassen²,

Aspeslagh

et al. 2016

Pathobiology

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Objective: Over the last decade, efforts have been made to get a better understanding of the tumor microenvironment and the role of the immune system in it. New insights into the CD27/CD70 signaling pathway point towards a role in tumor immunology, making CD70 an attractive target for immunotherapy. Here, we evaluate CD70 expression in squamous cell carcinoma of the head and neck (SCCHN). Methods: CD70 immunohistochemistry was retrospectively performed on 95 tumor samples. Tumoral CD70 expression was scored and correlated with clinicopathological variables and overall survival (OS). Results: CD70 expression in tumor cells was observed in 66 samples (69%) and was strongly associated with tumor differentiation grade (p < 0.001). CD70 expression was also observed in tumor-associated fibroblasts and endothelial cells. Additionally, the density of tumor-infiltrating lymphocytes correlated with OS (p = 0.042). Conclusion: This study describes the tumoral expression of CD70 in SCCHN. Results highlight the role of CD70 in tumor biology and identify CD70 as a novel therapeutic target. Further research is warranted.

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CD70: An emerging target in cancer immunotherapy

Cited by 148 publications

References 97 publications

PD-1 and PD-L1 blockade in gastrointestinal malignancies

PD-1 and PD-L1 blockade in gastrointestinal malignancies

Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers

CD70 Expression and Its Correlation with Clinicopathological Variables in Squamous Cell Carcinoma of the Head and Neck

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