An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer

Chu, Dinh‐Toi; Bac, Nguyen Duy; Nguyen, Khanh Hoang; Tien, Nguyen Le Bao; Thanh, Vo Van; Nga, Vu Thi; Ngọc, Võ Trương Như; Dao, Duong Thi Anh; Hoan, Le Ngoc; Hưng, Nguyễn Phúc; Thu, Nguyễn Thị Trung; Pham, Van Huy; Vũ, Lê Nguyên; Pham, Thuy Anh Vu; Raj, Deepak

doi:10.3390/ijms20081822

Cited by 70 publications

(69 citation statements)

References 99 publications

(188 reference statements)

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“…4-1BB therapy has entered into clinical trials involving GI cancer patients (NCT03330561). Poor efficacy and toxicity have been a concern in the past with 4-1BB therapy (128). Further preclinical studies are warranted.…”

Section: Preclinical Studies Targeting Cd73 and Adenosine Receptorsmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

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Section: Preclinical Studies Targeting Cd73 and Adenosine Receptorsmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

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“…CD137 ligand is a kind of transmembrane protein expressed on the cell surface. CD137 and CD137L form a bidirectional signaling pathway, which allows bidirectional signal exchange between receptor and ligand cells, thereby regulating their activities at the same time . CD137L is found on all types of antigen‐presenting cells .…”

Section: Biological Effects Of Cd137 Signalingmentioning

confidence: 99%

“…It can strongly activate CD8 + T cells, induce cytokine release, and increase CTL activity . Accumulating evidence has shown that anti‐CD137 mAbs could be used in cancer therapy alone or combined with other Abs or reagents . Recently, several related clinical trials have been carried out.…”

Section: Introductionmentioning

confidence: 99%

CD137, an attractive candidate for the immunotherapy of lung cancer

Jia

Wang

et al. 2020

Cancer Science

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Immunotherapy has become a hotspot in cancer therapy in recent years. Several immune checkpoints inhibitors have been used to treat lung cancer. CD137 is a kind of costimulatory molecule that mediates T cell activation, which regulates the activity of immune cells in a variety of physiological and pathological processes. Targeting CD137 or its ligand (CD137L) has been studied, aiming to enhance anticancer immune responses. Accumulating studies show that anti-CD137 mAbs alone or combined with other drugs have bright antitumor prospects. In the following, we reviewed the biology of CD137, the antitumor effects of anti-CD137 Ab monotherapy and the combined therapy in lung cancer. K E Y W O R D S anti-CD137 monoclonal antibody, CD137, CD137L, immune therapy, lung cancer How to cite this article: Ye L, Jia K, Wang L, et al. CD137, an attractive candidate for the immunotherapy of lung cancer.

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“…These molecules are important for tumor immunity, they are not only the target molecules of ICIs but are also responsible for resistance to anti‐cancer immunotherapy. Some researchers have attempted to overcome this resistance by combining ICIs or combining ICIs with immune stimulants such as TLR3 agonist or 4‐1BB . Currently, we are developing immunotherapy using CpG oligodeoxynucleotides (ODNs) for this purpose.…”

Section: Introductionmentioning

confidence: 99%

“…Some researchers have attempted to overcome this resistance by combining ICIs or combining ICIs with immune stimulants such as TLR3 agonist 7 or 4-1BB. 8 Currently, we are developing immunotherapy using CpG oligodeoxynucleotides (ODNs) for this purpose. Synthetic ODNs have various immunomodulatory effects.…”

Section: Introductionmentioning

confidence: 99%

Class A CpG oligodeoxynucleotide inhibits IFN‐γ‐induced signaling and apoptosis in lung cancer

et al. 2020

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Background Currently, anticancer immunotherapy based on PD‐1/PD‐L1 blockade with immune checkpoint inhibitors (ICIs) is being used as a standard therapy for non‐small cell lung cancer (NSCLC). However, more effective treatments are required as these tumors are often resistant and refractory. Here, we aimed to determine the effects of immunomodulatory oligodeoxynucleotides (ODNs) in terms of the presence or absence of CpG motifs and the number of consecutive guanosines. Methods Western blots were used to measure the molecules which regulate the expression of PD‐L1 in human lung cancer cell lines after incubation with several cytokines and ODNs. The expression of PD‐L1 and β2‐microglobulin (β2‐MG) on A549 cells, and IFN‐γ‐induced apoptosis with ODNs were examined by flow cytometry. The relationship between IFN‐γ receptor and ODN was analyzed by ELISA and immunofluorescence chemistry. Results Our results verified that A‐CpG ODNs suppress the upregulation of IFN‐γ‐induced PD‐L1 and β2‐MG expression. In addition, we found that ODNs with six or more consecutive guanosines (ODNs with poly‐G sequences) may competitively inhibit the IFN‐γ receptor and abolish the effect of IFN‐γ, thereby suppressing apoptosis and indoleamine 2,3‐dioxygenase 1 expression in human lung cancer cells. The tumor microenvironment regulates whether this action will promote or suppress tumor immunity. Thus, in immunotherapy with CpG ODNs, it is essential to consider the effect of ODNs with poly‐G sequences. Conclusions This study suggests that ODNs containing six or more consecutive guanosines may inhibit the binding of IFN‐γ to IFN‐γ receptor. However, it does not directly show that ODNs containing six or more consecutive guanosines competitively inhibit the IFN‐γ receptor, and further studies are warranted to confirm this finding. Key points Significant findings of the study: Oligodeoxynucleotides with a contiguous sequence of six or more guanosines may competitively inhibit the IFN‐γ receptor and abolish the action of IFN‐γ. This may suppress IFN‐γ‐induced apoptosis and indoleamine‐2,3‐dioxygenase‐1 expression in human lung cancer cells. What this study adds: A‐CpG and poly‐G ODN may overcome tolerance if the cause of ICI tolerance is high IDO expression. However, IFN‐γ also has the effect of suppressing apoptosis of cancer cells, and it is necessary to identify the cause of resistance.

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An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer

Cited by 70 publications

References 99 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD137, an attractive candidate for the immunotherapy of lung cancer

Class A CpG oligodeoxynucleotide inhibits IFN‐γ‐induced signaling and apoptosis in lung cancer

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