Next-generation cytokines for cancer immunotherapy

Xue, Diyuan; Hsu, Eric J.; Fu, Yang–Xin; Peng, Hua

doi:10.1093/abt/tbab014

Cited by 44 publications

(28 citation statements)

References 129 publications

(110 reference statements)

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“…Because GM-CSF might induce myeloid-derived suppressor cells [89,90], which has been observed in clinical trials [88], the application of GM-CSF should be carefully examined. Besides GM-CSF, cytokines such as IFN-α, IL-2, IL-15, IL-21, and IL-12 have been applied in preclinical and clinical studies [91]. The main drawback of directly supplying signal 3 in vivo is that cytokines have a short half-life and should be administered daily in large doses, which may cause severe toxicity and T-cell exhaustion [92].…”

Section: Modern Adjuvantsmentioning

confidence: 99%

Antitumor Peptide-Based Vaccine in the Limelight

et al. 2022

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The success of the immune checkpoint blockade has provided a proof of concept that immune cells are capable of attacking tumors in the clinic. However, clinical benefit is only observed in less than 20% of the patients due to the non-specific activation of immune cells by the immune checkpoint blockade. Developing tumor-specific immune responses is a challenging task that can be achieved by targeting tumor antigens to generate tumor-specific T-cell responses. The recent advancements in peptide-based immunotherapy have encouraged clinicians and patients who are struggling with cancer that is otherwise non-treatable with current therapeutics. By selecting appropriate epitopes from tumor antigens with suitable adjuvants, peptides can elicit robust antitumor responses in both mice and humans. Although recent experimental data and clinical trials suggest the potency of tumor reduction by peptide-based vaccines, earlier clinical trials based on the inadequate hypothesis have misled that peptide vaccines are not efficient in eliminating tumor cells. In this review, we highlighted the recent evidence that supports the rationale of peptide-based antitumor vaccines. We also discussed the strategies to select the optimal epitope for vaccines and the mechanism of how adjuvants increase the efficacy of this promising approach to treat cancer.

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Section: Modern Adjuvantsmentioning

confidence: 99%

Antitumor Peptide-Based Vaccine in the Limelight

et al. 2022

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“…The IL-2Rβ/γ receptor is expressed on naïve CD8 and memory CD4 and CD8 T-cells. While all 3 subunits of the IL-2 receptor (IL-2Rα/β/γ) are found on activated CD4 and CD8 T-cells ( 7 ), high expression of IL-2Rα is a defining characteristic of Tregs ( 8 ). The presence of IL-2Rα significantly increases the binding affinity of IL-2 for its receptor.…”

Section: Il-2mentioning

confidence: 99%

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Wolfarth¹,

Dhar²,

Goon³

et al. 2022

Immune Netw

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The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short half-life of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

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“…In addition to IFN α , cytokines such as IL-12, IL-15, IL-21, and IFN β are currently undergoing clinical testing [ 13 , 14 ]. Much like IL-2 therapy, these cytokines are limited by half-life, toxicities, and low efficacy which has warranted the development of next-generation versions [ 15 ].…”

Section: Il-2 In Cancer Immunotherapymentioning

confidence: 99%

Interleukin 2-Based Fusion Proteins for the Treatment of Cancer

MacDonald

Hung

2021

Journal of Immunology Research

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Interleukin 2 (IL-2) plays a fundamental role in both immune activation and tolerance and has revolutionized the field of cancer immunotherapy since its discovery. The ability of IL-2 to mediate tumor regression in preclinical and clinical settings led to FDA approval for its use in the treatment of metastatic renal cell carcinoma and metastatic melanoma in the 1990s. Although modest success is observed in the clinic, cancer patients receiving IL-2 therapy experience a wide array of side effects ranging from flu-like symptoms to life-threatening conditions such as vascular leak syndrome. Over the past three decades, efforts have focused on circumventing IL-2-related toxicities by engineering methods to localize IL-2 to the tumor or secondary lymphoid tissue, preferentially activate CD8+ T cells and NK cells, and alter pharmacokinetic properties to increase bioavailability. This review summarizes the various IL-2-based strategies that have emerged, with a focus on chimeric fusion methods.

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Next-generation cytokines for cancer immunotherapy

Cited by 44 publications

References 129 publications

Antitumor Peptide-Based Vaccine in the Limelight

Antitumor Peptide-Based Vaccine in the Limelight

Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

Interleukin 2-Based Fusion Proteins for the Treatment of Cancer

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