Abstract Breakthroughs in molecular mechanisms underlying immune-suppressive tumor microenvironment and paradigm shifts in the cancer-immunity response cycle have profoundly changed the landscape of cancer immunotherapy. However, one of the challenges is to mitigate the serious side effects caused by systemic autoimmunity and autoinflammatory responses following immunotherapy. Thus, restraining the activation of the immune system in healthy tissues is highly desirable to address this problem. Bioengineering and delivery technologies provide a solution to the issue. In this Review, we first introduce immune-related adverse effects of main immunotherapies and the underlying mechanisms, summarize various strategies to construct bioengineering and delivery systems in order to reduce their immunotoxicities, and highlight the importance for the development of immunotoxicity-related animal models.
Last. Yuxia Luan(SDU: Shandong University)H-Index: 29
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Abstract Immune checkpoint blockade (ICB) strategy based on suppressing programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has been proved to be promising and effective in cancer immunotherapy. However, its potential risk of immune-related adverse events (irAEs) places stringent requirements on the precise loading of anti-PD-L1 agent in nanomedicine. Precise control of the loading content of anti-PD-L1 antibody is a difficult task since physical encapsulation has inevitable draw...
Abstract Tumor microenvironment (TME) closely affects cancer progression by promoting cancer cell survival and proliferation, drug resistance, metastasis, and immunosuppression as well. Remodeling TME is a promising therapeutic strategy for anticancer. mTOR signaling is an essential regulator for cellular metabolism and tumor-associated macrophages (TAMs) repolarization. There is an integrated crosstalk among mTOR/metabolism/immunity. Angiogenesis can also regulate metabolism and immunity. Based...
#1Adi Diab(University of Texas MD Anderson Cancer Center)H-Index: 32
#2Nizar M. Tannir(University of Texas MD Anderson Cancer Center)H-Index: 57
Last. Daniel C. Cho(NYU: New York University)H-Index: 17
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This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempegaldesleukin (NKTR-214/BEMPEG), a CD122-preferential IL2 pathway agonist, plus nivolumab in 38 patients with selected immunotherapy-naive advanced solid tumors (melanoma, renal cell carcinoma, and non–small cell lung cancer). Three dose-limiting toxicities were reported in 2 of 17 patients during dose escalation [hypotension (n = 1), hyperglycemia (n = 1), metabolic acidosis (n = 1)]. The most common treatment-related ...
Last. Honggang Cui(Johns Hopkins University)H-Index: 45
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Immune checkpoint blockers (ICBs) have shown great promise at harnessing immune system to combat cancer. However, only a fraction of patients can directly benefit from the anti–programmed cell death protein 1 (aPD1) therapy, and the treatment often leads to immune-related adverse effects. In this context, we developed a prodrug hydrogelator for local delivery of ICBs to boost the host’s immune system against tumor. We found that this carrier-free therapeutic system can serve as a reservoir for e...
#1Zhaoting Li(CPU: China Pharmaceutical University)H-Index: 4
#2Yixin Wang(CPU: China Pharmaceutical University)H-Index: 6
Last. Minjie Sun(CPU: China Pharmaceutical University)H-Index: 25
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Anti–programmed cell death 1 ligand 1 (PD-L1) therapy is extraordinarily effective in select patients with cancer. However, insufficient lymphocytic infiltration, weak T cell–induced inflammation, and immunosuppressive cell accumulation in the tumor microenvironment (TME) may greatly diminish the efficacy. Here, we report development of the FX@HP nanocomplex composed of fluorinated polymerized CXCR4 antagonism (FX) and paclitaxel-loaded human serum albumin (HP) for pulmonary delivery of anti–PD-...
The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an ef...
Checkpoint-inhibitor (CPI) immunotherapy has achieved remarkable clinical success, yet its efficacy in ‘immunologically cold’ tumours has been modest. Interleukin-12 (IL-12) is a powerful cytokine that activates the innate and adaptive arms of the immune system; however, the administration of IL-12 has been associated with immune-related adverse events. Here we show that, after intravenous administration of a collagen-binding domain fused to IL-12 (CBD–IL-12) in mice bearing aggressive mouse tum...
Immune checkpoint inhibitor (ICI) therapy has shown a significant benefit in the treatment of a variety of cancer entities. However, immune-related adverse events (irAEs) occur frequently and can lead to ICI treatment termination. MicroRNA-146a (miR-146a) has regulatory functions in immune cells. We observed that mice lacking miR-146a developed significantly more severe irAEs compared to wildtype mice in several irAE target organs in two different murine models. MiR-146a-/- mice exhibited increa...
Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicitie...
Last. In-San Kim(Kigali Institute of Science and Technology)H-Index: 60
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Abstract Cancer immunotherapy (CI) represented by immune checkpoint inhibitors (ICIs) presents a new paradigm for cancer treatment. However, the types of cancer that attain a therapeutic benefit from ICIs are limited, and the efficacy of these treatments does not meet expectations. To date, research on ICIs has mainly focused on identifying biomarkers and patient characteristics that can enhance the therapeutic effect on tumors. However, studies on combinational strategies for CI are being activ...
#2Jianfeng Zhou(Peking Union Medical College Hospital)
Last. Chunmei Bai(Peking Union Medical College Hospital)H-Index: 7
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Immune checkpoint inhibitor (ICI) is a revolutionary breakthrough in the field of cancer treatment. Because of dysregulated activation of the immune system, patients with autoimmune disease (AID) are usually excluded from ICI clinical trials. Due to a large number of cancer patients with preexisting AID, the safety and efficacy of ICIs in these patients deserve more attention. This review summarizes and analyzes the data regarding ICI therapy in cancer patients with preexisting AID from 17 publi...