ImmunoTar-integrative prioritization of cell surface targets for cancer immunotherapy.

Rawan Shraim, Brian Mooney, Karina L Conkrite, Amber K Hamilton, Gregg B Morin, Poul H Sorensen, John M Maris, Sharon J Diskin, Ahmet Sacan
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Abstract

Motivation: Cancer remains a leading cause of mortality globally. Recent improvements in survival have been facilitated by the development of targeted and less toxic immunotherapies, such as chimeric antigen receptor (CAR)-T cells and antibody-drug conjugates (ADCs). These therapies, effective in treating both pediatric and adult patients with solid and hematological malignancies, rely on the identification of cancer-specific surface protein targets. While technologies like RNA sequencing and proteomics exist to survey these targets, identifying optimal targets for immunotherapies remains a challenge in the field.

Results: To address this challenge, we developed ImmunoTar, a novel computational tool designed to systematically prioritize candidate immunotherapeutic targets. ImmunoTar integrates user-provided RNA-sequencing or proteomics data with quantitative features from multiple public databases, selected based on predefined criteria, to generate a score representing the gene's suitability as an immunotherapeutic target. We validated ImmunoTar using three distinct cancer datasets, demonstrating its effectiveness in identifying both known and novel targets across various cancer phenotypes. By compiling diverse data into a unified platform, ImmunoTar enables comprehensive evaluation of surface proteins, streamlining target identification and empowering researchers to efficiently allocate resources, thereby accelerating the development of effective cancer immunotherapies.

Availability and implementation: Code and data to run and test ImmunoTar are available at https://github.com/sacanlab/immunotar.

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肿瘤免疫治疗中细胞表面靶点的免疫靶向整合优先排序。
动机:癌症仍然是全球死亡的主要原因。最近生存率的提高得益于靶向性和毒性较低的免疫疗法的发展,如嵌合抗原受体(CAR)-T细胞和抗体-药物偶联物(adc)。这些疗法,有效治疗儿童和成人实体和血液系统恶性肿瘤患者,依赖于癌症特异性表面蛋白靶点的鉴定。虽然存在RNA测序和蛋白质组学等技术来调查这些靶点,但确定免疫治疗的最佳靶点仍然是该领域的一个挑战。为了应对这一挑战,我们开发了一种新的计算工具immune - notar,旨在系统地优先考虑候选免疫治疗靶点。immnotar将用户提供的rna测序或蛋白质组学数据与来自多个公共数据库的定量特征相结合,根据预定义的标准选择,生成一个代表基因作为免疫治疗靶点的适用性的评分。我们使用三种不同的癌症数据集验证了immnotar,证明了其在识别各种癌症表型的已知和新靶点方面的有效性。通过将不同的数据汇编到一个统一的平台上,ImmunoTar可以对表面蛋白进行综合评估,简化靶标识别,使研究人员能够有效地分配资源,从而加速开发有效的癌症免疫疗法。可用性:运行和测试immunar的代码和数据可在https://github.com/sacanlab/immunotar.Supplementary上获得。信息:补充数据可在Bioinformatics在线上获得。
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