To respond or not to respond to CD40 agonism: That is the prediction

Shi, Xiaoyan; Dornan, David

doi:10.4161/onci.1.1.17827

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…It can promote apoptosis and stimulate angiogenesis and transcription/secretion of matrix metalloproteinase. 28 , 29 In addition, it has been reported that CD40 upregulates the expression of ICAM-1, 30 a cell-adhesion molecule important for cell–cell interactions. These programs are closely related to the migration and invasion of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)

Song¹,

Ni²,

Zou³

et al. 2016

OTT

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ObjectivesThe objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).Design and methodsThe immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.ResultsThe results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB) type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS) and progression-free survival (PFS) in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS.ConclusionOur findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP.

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Section: Discussionmentioning

confidence: 99%

Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)

Song¹,

Ni²,

Zou³

et al. 2016

OTT

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“…interleukin-2, interferon-α) [34][35][36] • Killer-cell immunoglobulin-like receptor antagonists [37] • Indoleamine 2,3-dioxygenase (IDO) pathway inhibitors [38] Therapeutic vaccines • Sipuleucel-T (prostate carcinoma) [39] • Anti-MAGE-A3 vaccine (non-small cell lung cancer and others) [40] • Racotumomab -anti N-glycolyl (lung carcinoma, breast carcinoma, melanoma) [41] • Tergenpumatucel-L (lung carcinoma) [42] Modulate T-cell function • CD137 agonism [43] • CD40 agonism [44] • CTLA-4 inhibition [45] • LAG-3 inhibition [46] • OX-40 agonism [47] • PD-1 inhibition [48] • PD-L1 inhibition [49] • PD-L2 inhibition [50,51] Oncolytic viruses • Talimogene laherparepvec (T-VEC, melanoma) [52] against CTLA-4 such as ipilimumab have been shown to be effective as single agents, with some durable clinical responses noted [45]. PD-1 is an inhibitory receptor expressed on T-cells whose normal function is crucial for preventing the development of autoimmune disease [62].…”

Section: Immunotherapeutic Approaches In the Treatment Of Cancermentioning

confidence: 99%

“…Active approaches include non-specific immune modulation, therapeutic vaccines, modulation of T-cell function and oncolytic viruses. Examples of these are shown in Table 1 [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52].…”

Section: Immunotherapeutic Approaches In the Treatment Of Cancermentioning

confidence: 99%

Immune modulation in advanced radiotherapies: Targeting out-of-field effects

2015

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By virtue of being a localized treatment modality, radiotherapy is unable to deliver a tumoricidal radiation dose to tissues outside of the irradiated field. Nevertheless, ionizing radiation may result in radiation damage mediated by a bystander like effect away from the irradiated field, but this response is likely to be modest when radiotherapy is the sole treatment modality. Over the last decade there has been a re-emergence of immune modulating therapies as anti-cancer treatment modalities. Clinical trials on vaccines have on the whole been largely disappointing, but greater response rates have been observed from the immune checkpoint modulators. A clinical benefit of using such agents has been shown in disease sites such as melanoma and non-small cell lung cancer. There is growing pre-clinical data and a number of case reports which suggest the presence of abscopal effects when radiotherapy is co-administered with immune checkpoint inhibitors, suggesting that this combination may lead to an enhanced tumour response outside of the primary treatment field. In this review, the mechanisms of such an enhanced out-of-field tumour response, the potential clinical utilities, the optimal radiotherapy delivery and considerations for clinical follow-up following treatment are discussed.

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The Use of Anti-CD40 mAb in Cancer

Remer

White

Glennie

et al. 2014

Current Topics in Microbiology and Immunology

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Immunomodulatory monoclonal antibody (mAb) therapy is at the forefront of developing cancer therapeutics with numerous targeted agents proving highly effective in selective patients at stimulating protective host immunity, capable of eradicating established tumours and leading to long-term disease-free states. The cell surface marker CD40 is expressed on a range of immune cells and transformed cells in malignant states whose signalling plays a critical role in modulating adaptive immune responses. Anti-CD40 mAb therapy acts via multiple mechanisms to stimulate anti-tumour immunity across a broad range of lymphoid and solid malignancies. A wealth of preclinical research in this field has led to the successful development of multiple anti-CD40 mAb agents that have shown promise in early-phase clinical trials. Significant progress has been made to enhance the engagement of antibodies with immune effectors through their interactions with Fcγ receptors (FcγRs) by the process of Fc engineering. As more is understood about how to best optimise these agents, principally through the fine-tuning of mAb structure and choice of synergistic partnerships, our ability to generate robust, clinically beneficial anti-tumour activity will form the foundation for the next generation of cancer therapeutics.

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To respond or not to respond to CD40 agonism: That is the prediction

Cited by 4 publications

References 11 publications

Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)

Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)

Immune modulation in advanced radiotherapies: Targeting out-of-field effects

The Use of Anti-CD40 mAb in Cancer

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