A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors

Xue, Diyuan; Moon, Benjamin; Liao, Jing; Guo, Jingya; Zou, Zhuangzhi; Han, Yanfei; Cao, Shuaishuai; Wang, Yang; Fu, Yang–Xin; Peng, Hua

doi:10.1126/sciimmunol.abi6899

Cited by 55 publications

(37 citation statements)

References 68 publications

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“…However, the level of these cytokines was negligible to be detected in peripheral blood after 24 h of the final treatment, indicating the combination therapy could not cause systemic cytokine storms. [ 46 ] Therefore, these results demonstrate that combined PTT‐immunotherapy has the potential to completely eradicate the primary tumors, as well as significantly suppress abscopal tumors by eliciting robust systemic antitumor immunity.…”

Section: Resultsmentioning

confidence: 83%

Nanoplatform Self‐Assembly from Small Molecules of Porphyrin Derivatives for NIR‐II Fluorescence Imaging Guided Photothermal‐Immunotherapy

Cao

Yang

et al. 2022

Adv Healthcare Materials

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Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts with many limitations, such as complex components, sophisticated construction and inadequate therapeutic e cacy. In this work, we develop small molecules of porphyrin derivatives (PPor) which can selfassemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants.The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originated from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II uorescence imaging guided photothermal therapy (PTT) against primary tumor with a high cure rate. More importantly, tumor-associated antigens (TAAs) together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells are proved to elicit immune responses in some degree. After combination with programmed cell death-1 (PD-1) antibody, a robust systematic antitumor immunity are generated to restrain both primary and abscopal tumors growth, prolong survival, prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumor with high e ciency.

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Section: Resultsmentioning

confidence: 83%

Nanoplatform Self‐Assembly from Small Molecules of Porphyrin Derivatives for NIR‐II Fluorescence Imaging Guided Photothermal‐Immunotherapy

Cao

Yang

et al. 2022

Adv Healthcare Materials

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“…IL-2 and IL-12 can effectively fight the disease when co-transfected in tumor cells, which provides a promising immunotherapy approach for the treatment of NB, CD4+ and CD8+ T cells can mediate this reaction (31). Fibroblasts co-transfected with homologous IL-2 and IL-12 not only have therapeutic effects on diseases, but also can produce immune memory (32). Co-injection of IL-2 and IL-12 co-expressed fibroblasts and ex vivo transfected tumor cells with Neuro-2A tumor cells, which eliminated the tumorigenicity in patients with three intratumoral doses treatment with transfected fibroblasts has a significant curative effect, and the cure rate can reach 90% (33).…”

Section: Il-2mentioning

confidence: 99%

Cytokine Immunotherapy for Neuroblastoma

Dowsey

2023

Sci Insights

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Neuroblastoma (NB) is an embryonal tumor originating from the sympathetic nervous system, which occurs during fetal period or early postnatal period, and is one of the most common extracranial solid malignant tumors in children. Cytokines are pleiotropic proteins that can effectively activate tumor immune cells and counteract immune suppression, thereby suppressing tumors. Cytokine immunotherapy provides more possibilities for the application of immunotherapy through its own induction and activation of the immune system and has also been extensively studied in NB immunotherapy. This article mainly introduces the research progress of several immunotherapies based on cytokines in the treatment of children with NB.

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“…Inflammatory cytokines generally upregulate the expression, secretion and activation of MPs in immune cells (11,171,172). In addition, they are shed as substrates or become active after cleavage by MPs leading to various immune-inflammatory responses in multiple cancers (12,173,174).…”

Section: Immunomodulatory Substances Associated With Mpsmentioning

confidence: 99%

Immunomodulatory role of metalloproteases in cancers: Current progress and future trends

Wang

Wang²,

Tan³

et al. 2022

Front. Immunol.

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Metalloproteinases (MPs) is a large family of proteinases with metal ions in their active centers. According to the different domains metalloproteinases can be divided into a variety of subtypes mainly including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteases (ADAMs) and ADAMs with Thrombospondin Motifs (ADAMTS). They have various functions such as protein hydrolysis, cell adhesion and remodeling of extracellular matrix. Metalloproteinases expressed in multiple types of cancers and participate in many pathological processes involving tumor genesis and development, invasion and metastasis by regulating signal transduction and tumor microenvironment. In this review, based on the current research progress, we summarized the structure of MPs, their expression and especially immunomodulatory role and mechanisms in cancers. Additionally, a relevant and timely update of recent advances and future directions were provided for the diagnosis and immunotherapy targeting MPs in cancers.

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A tumor-specific pro-IL-12 activates preexisting cytotoxic T cells to control established tumors

Abstract: A tumor-specific pro-IL-12 rejuvenated preexisting TILs to induce tumor growth delay without inducing systemic toxicity.

Cited by 55 publications

References 68 publications

Nanoplatform Self‐Assembly from Small Molecules of Porphyrin Derivatives for NIR‐II Fluorescence Imaging Guided Photothermal‐Immunotherapy

Nanoplatform Self‐Assembly from Small Molecules of Porphyrin Derivatives for NIR‐II Fluorescence Imaging Guided Photothermal‐Immunotherapy

Cytokine Immunotherapy for Neuroblastoma

Immunomodulatory role of metalloproteases in cancers: Current progress and future trends

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