The latest advancements in oncology are majorly focused on immuno-oncology (I-O) therapies. However, only ∼7% of drugs are being approved from the preclinical discovery phase to phase 1. The most challenging issues in I-O are the development of active and efficient drugs in an economically feasible way and in a comparatively short time for testing and validation. This mandates an urgent need for the upgradation of preclinical screening models that closely mimic the in vivo tumor microenvironment (TME). The established and most common methods for investigating the tumoricidal activity of I-O drugs are either two-dimensional systems or primary tumor cells in standard tissue culture vessels. Unfortunately, they do not mimic the TME. Consequently, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell-mediated responses in reaction to the administration of I-O drugs. Despite many advantages of multicellular spheroids, challenges (e.g., incompatibility of quantitative assays with spheroid platforms) are still involved in the tedious procedures required for the spheroid culture that is holding back the biological community from adapting the well-recognized spheroid tissue models for studying drug delivery more widely. To this end, we have demonstrated the utility of the 3D ex vivo oncology model, developed on our novel AXTEX-4D^™ platform to assess therapeutic efficacies of I-O drugs by investigating immune cell proliferation, migration, infiltration, cytokine profiling, and cytotoxicity of tumor tissueoids. The platform eliminates the need for additional biomolecules such as hydrogels and instead relies on the cancer cells themselves to create their own gradients and microenvironmental factors. In effect, the more comprehensive and ex vivo-like immune-oncology model developed on AXTEX-4D platform can be utilized for high-throughput screening of immunotherapeutic drugs.

中文翻译：

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AXTEX-4D：用于免疫治疗药物临床前研究的三维体外平台

肿瘤学的最新进展主要集中在免疫肿瘤学 (IO) 疗法上。然而，从临床前发现阶段到第一阶段，只有 7% 的药物获得批准。IO 中最具挑战性的问题是以经济可行的方式开发活性和高效的药物，并在相对较短的时间内进行测试和验证。这就迫切需要升级与体内肿瘤微环境 (TME) 密切相似的临床前筛选模型。研究 IO 药物的杀肿瘤活性的既定和最常见的方法是二维系统或标准组织培养容器中的原发性肿瘤细胞。不幸的是，它们并没有模仿 TME。因此，体内越类似三维 (3D) 的多细胞肿瘤球体正迅速成为检测免疫细胞介导的对 IO 药物给药反应的首选模型。尽管多细胞球体有许多优点，但挑战（例如，定量测定与球体平台的不相容性）仍然涉及球体培养所需的繁琐程序，这阻碍了生物群落适应公认的球体组织模型来研究药物交付范围更广。为此，我们展示了基于我们的新型 AXTEX-4D ^{™开发的 3D}离体肿瘤学模型的实用性通过研究免疫细胞增殖、迁移、浸润、细胞因子分析和肿瘤组织样的细胞毒性来评估 IO 药物治疗效果的平台。该平台消除了对水凝胶等额外生物分子的需求，而是依靠癌细胞本身来创建自己的梯度和微环境因素。实际上，在 AXTEX-4D 平台上开发的更全面和离体免疫肿瘤学模型可用于免疫治疗药物的高通量筛选。