Antibody-Based Immunotherapy of Solid Cancers: Progress and Possibilities

Nicodemus, Christopher F.

doi:10.2217/imt.15.57

Cited by 24 publications

(18 citation statements)

References 78 publications

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“…Importantly, the definition of the best candidates able to induce ELN needs to take into account the considerably immunosuppressive environment characterizing neoplastic processes . Nevertheless, the clinical success of checkpoint inhibitors in the treatment of solid tumors has validated the approach of modulating natural immune responses as anticancer therapy …”

Section: Cancer: New Insightsmentioning

confidence: 99%

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

Nerviani

Pitzalis

2018

Journal of Leukocyte Biology

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Ectopic (or tertiary) lymphoid structures (ELS) are organized aggregates of lymphocytes resembling secondary lymphoid organs and developing in chronically inflamed nonlymphoid tissues during persistent infections, graft rejection, autoimmune conditions, and cancer. In this review, we will first depict the mechanisms regulating ELS generation, focusing on the role played by lymphoid chemokines. We will then characterize ELS forming in target organs during autoimmune conditions, here exemplified by rheumatoid arthritis, and cancer, highlighting the relevance of the tissue‐specific factors. Finally, we will discuss the clinical significance of ELS and the therapeutic potential of their inhibition and/or enhancement depending on the disease considered.

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Section: Cancer: New Insightsmentioning

confidence: 99%

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

Nerviani

Pitzalis

2018

Journal of Leukocyte Biology

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“…TIM-3 binds to its ligand galectin-9, which can induce apoptosis in Th1 cells to downregulate effector Th1/Tc1 cell responses and suppress, as well as induce, peripheral tolerance ( 13 , 14 ). Monoclonal antibodies can block the immune checkpoint pathway, which acts on T-cell inhibitory or immune checkpoint receptors; immunotherapy has demonstrated as an effective strategy for the treatment of cancer ( 15 ). TIM-3 is expressed by the majority of suppressed or dysfunctional T cell populations, including CD8 + T cells and Tregs, which exert key roles in immunosuppression in tumor tissue based on preclinical trials ( 16 – 18 ).…”

Section: Introductionmentioning

confidence: 99%

T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

Hou

et al. 2017

Oncol Lett

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The aim of the present study was to investigate the expression levels of the T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) and galectin-9 proteins and their clinical value in esophageal squamous cell carcinoma (ESCC) in Chinese patients. The expression profiles of TIM-3 and galectin-9 in ESCC were determined by the immunohistochemical analysis of the postoperative pathological specimens of 45 patients with ESCC; a χ2 test was used to evaluate the association of TIM-3 and galectin-9 expression with clinicopathological parameters, in addition to univariate and multivariate Cox's proportional hazards model to analyze the prognostic value of the expression of TIM-3 and galectin-9 proteins. The proportion of samples exhibiting a high staining intensity for TIM-3 and galectin-9 were 22.22 and 15.56%, respectively: these samples were termed the TIM-3 high-expression group (HEG) and galectin-9-HEG. There was a negative correlation between the expression of TIM-3 and galectin-9 (R=−0.71, P<0.001). The results of Kaplan-Meier survival analysis led to the conclusion that, compared with the TIM-3 low expression group (LEG), patients in the TIM-3-HEG exhibited a poorer overall survival rate (χ2=6.049, P=0.0139). By contrast, patients in the galectin-9-HEG exhibited a significantly better overall survival rate than those in the galectin-9-LEG (χ2=4.915, P=0.0266). However, the levels of TIM-3 and galectin-9 expression were not identified as independent indicators for the prognosis of patients with ESCC. As high TIM-3 and low galectin-9 expression levels were associated with a poor prognosis for patients with ESCC in the present study, these proteins may be potential prognostic indicators for ESCC.

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“…Antibody-based treatments are a promising approaches in cancer immunotherapy and emerged due to their high degree of specificity to target precision sites implicated in cancer development [65]. However, there is a need for novel delivery strategies to reach the highest levels of specificity in antibody targeting, while trying to avoid off-target side effects as much as possible.…”

Section: Hybrid Nanocarriersmentioning

confidence: 99%

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

Al-Hatamleh

Boer

et al. 2019

Cells

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Tumor necrosis factor receptor 2 (TNFR2) is expressed on some tumor cells, such as myeloma, Hodgkin lymphoma, colon cancer and ovarian cancer, as well as immunosuppressive cells. There is increasingly evidence that TNFR2 expression in cancer microenvironment has significant implications in cancer progression, metastasis and immune evasion. Although nanomedicine has been extensively studied as a carrier of cancer immunotherapeutic agents, no study to date has investigated TNFR2-targeting nanomedicine in cancer treatment. From an epigenetic perspective, previous studies indicate that DNA demethylation might be responsible for high expressions of TNFR2 in cancer models. This perspective review discusses a novel therapeutic strategy based on nanomedicine that has the capacity to target TNFR2 along with inhibition of DNA demethylation. This approach may maximize the anti-cancer potential of nanomedicine-based immunotherapy and, consequently, markedly improve the outcomes of the management of patients with malignancy.Cells 2020, 9, 33 2 of 16 and tumor cells [6][7][8]. In contrast, TNFR2 expression was only reported on tumor cells and suppressive immune cells, suggesting that TNFR2 directly promotes cancer development [9]. Furthermore, the latest preclinical and clinical studies confirmed the implication of TNF-TNFR2 signaling in cancer proliferation and the suppression of immune response [10,11]. Consequently, blockade of TNF-TNFR2 axis could be a promising option for cancer treatment (Figure 1).On the other hand, nanotechnology provided several platforms in the field of immunotherapy and made significant advances towards safe and efficient targeting systems with positive clinical outcomes and minimal side effects; this is the so-called field of nanomedicine [12]. Despite the emerging trends of using nanoparticles in immunotherapy, no studies have investigated any type of nanocarriers to target TNFR2 on cancer cells. However, based on some previous novel reports about the effects of nanoparticles on immune homeostasis [13], especially using nanoparticles to promote TNFR2 + Foxp3 + regulatory T cells (Tregs) in inflammatory models [14,15], we have suggested in our recent perspective review the possibility of blocking TNF-TNFR2 axis via nanoparticles [16].

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Antibody-Based Immunotherapy of Solid Cancers: Progress and Possibilities

Cited by 24 publications

References 78 publications

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer

T‑cell immunoglobulin and mucin domain‑containing protein‑3 and galectin‑9 protein expression: Potential prognostic significance in esophageal squamous cell carcinoma for Chinese patients

Synergistic Effects of Nanomedicine Targeting TNFR2 and DNA Demethylation Inhibitor—An Opportunity for Cancer Treatment

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