Dataset Information

IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines.

ABSTRACT: Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of IL-12 post administration. In this regard, we have developed a cell membrane-anchored and tumor-targeted IL-12-T (attIL12-T) cell product for avoiding toxicity from both IL-12 and T cells-induced cytokine release syndrome in peripheral tissues. A phase I trial using this product which seeks to avoid systemic toxicity and boost antitumor efficacy is on the horizon. Of note, this product also boosts the impact of CAR-T or TCR-T cell efficacy against solid tumors, providing an alternative approach to utilize CAR-T to overcome tumor resistance.

SUBMITTER: Jia Z

PROVIDER: S-EPMC9530253 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines.

Jia Zhiliang Z Ragoonanan Dristhi D Mahadeo Kris Michael KM Gill Jonathan J Gorlick Richard R Shpal Elizabeth E Li Shulin S

Frontiers in immunology 20220920

Interleukin 12 (IL-12) is a naturally occurring cytokine that plays a key role in inducing antitumor immune responses, including induction of antitumor immune memory. Currently, no IL-12-based therapeutic products have been approved for clinical application because of its toxicities. On the basis of this review of clinical trials using primarily wild-type IL-12 and different delivery methods, we conclude that the safe utilization of IL-12 is highly dependent on the tumor-specific localization of ...[more]

PMID: 36203573

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Project description:Chimeric antigen receptor T-cell (CAR-T) immunotherapy, a novel approach for treating blood cancer, is associated with the production of cytokine release syndrome (CRS), which poses significant safety concerns for patients. Currently, there is limited knowledge regarding CRS-related cytokines and the intricate relationship between cytokines and cells. Therefore, it is imperative to explore a reliable and efficient computational method to identify cytokines associated with CRS. In this study, we propose Meta-DHGNN, a directed and heterogeneous graph neural network analysis method based on meta-learning. The proposed method integrates both directed and heterogeneous algorithms, while the meta-learning module effectively addresses the issue of limited data availability. This approach enables comprehensive analysis of the cytokine network and accurate prediction of CRS-related cytokines. Firstly, to tackle the challenge posed by small datasets, a pre-training phase is conducted using the meta-learning module. Consequently, the directed algorithm constructs an adjacency matrix that accurately captures potential relationships in a more realistic manner. Ultimately, the heterogeneous algorithm employs meta-photographs and multi-head attention mechanisms to enhance the realism and accuracy of predicting cytokine information associated with positive labels. Our experimental verification on the dataset demonstrates that Meta-DHGNN achieves favorable outcomes. Furthermore, based on the predicted results, we have explored the multifaceted formation mechanism of CRS in CAR-T therapy from various perspectives and identified several cytokines, such as IFNG (IFN-γ), IFNA1, IFNB1, IFNA13, IFNA2, IFNAR1, IFNAR2, IFNGR1 and IFNGR2 that have been relatively overlooked in previous studies but potentially play pivotal roles. The significance of Meta-DHGNN lies in its ability to analyze directed and heterogeneous networks in biology effectively while also facilitating CRS risk prediction in CAR-T therapy.

Dataset Information

IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines.

Publications

IL12 immune therapy clinical trial review: Novel strategies for avoiding CRS-associated cytokines.

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