Aug 2026· International Journal for Sciences and Technology· 0 citations· 73 references
TL;DR
Collectively, CRISPR-driven immune engineering represents a paradigm shift toward more precise, effective, and accessible cancer immunotherapies.
Abstract
Immuno-oncology has reshaped the therapeutic landscape of cancer treatment by shifting focus from directly targeting tumor cells to mobilizing the immune system against malignancies. Among the most transformative advances in this field is the development of chimeric antigen receptor T-cell therapy, which has demonstrated remarkable efficacy in hematologic cancers. However, persistent challenges such as limited durability, immune escape, toxicity, and poor performance in solid tumors have constrained its broader clinical impact. The emergence of clustered regularly interspaced short palindromic repeats (CRISPR) genome editing has introduced a powerful and versatile platform for engineering immune cells with enhanced specificity, persistence, and functionality. CRISPR-based approaches enable precise gene knockout, targeted gene insertion, epigenetic modulation, and multiplex editing, allowing researchers to redesign immune cells at multiple regulatory levels. These capabilities have significantly advanced CAR-T cell engineering and have catalyzed the development of next-generation immune effectors, including natural killer cells, macrophages, and stem cell-derived immune populations. Furthermore, CRISPR technology has opened new avenues for overcoming the immunosuppressive tumor microenvironment, improving safety profiles, and enabling scalable, off-the-shelf therapies. This review provides a comprehensive examination of CRISPR applications in immuno-oncology, with an emphasis on CAR-T optimization and the engineering of next-generation immune cells. It discusses mechanistic foundations, technological innovations, preclinical and clinical advancements, safety considerations, and future directions. Collectively, CRISPR-driven immune engineering represents a paradigm shift toward more precise, effective, and accessible cancer immunotherapies.
A recent major breakthrough in cancer immunotherapy is the Chimeric antigen receptor-T cell (CAR-T cell) therapy, which has shown significant clinical efficacy in haematological malignancy treatment. Nonetheless, its application in a more general way is limited by a number of challenges, such as T-cell exhaustion, off-target associated toxicities, and the difficulty of personalised manufacturing. Recently, new opportunities have come into solving these problems with the introduction of clustered regularly interspaced short tandem repeats (CRISPR)-Cas9 genome editing, which has made it possible to perform precise and combinatorial genetic editing in CAR-T cells. The important applications of CRISPR in CAR-T cell engineering, which include the disruption of inhibitory immune checkpoints to enhance antitumour activity, the generation of universal allogeneic CAR-T cells by deletion of T-cell receptor and human leukocyte antigen (HLA) genes, and the modulation of cytokine signalling pathways to reduce toxicity are discussed in this review. Moreover, novel approaches, including targeted CAR integration and multiplex gene editing, are discussed as having the potential to enhance the therapeutic efficacy and scalability. In spite of these improvements, there are issues of off-target effect, delivery efficacy, genomic instability, and unaddressed issues of long-term safety. CAR-T cell therapies are likely to be improved further in future through advancements in genome editing technology, delivery methods, and synthetic biology. In general, CRISPR/Cas9-based engineering is a promising way of developing the next generation of precision cancer immunotherapy.
Meng-Ying Liu· International Journal of Bio...· 0 citations
The biological mechanisms underlying resistance to CAR-T therapy in solid tumors are examined and emerging combination strategies designed to enhance tumor recognition, trafficking, persistence, and antitumor activity are critically evaluated.
Wei Cheng, Mei-Lan Liu, Yu-Hua Diao et al.· Cancer Biome and Targeted Th...· 0 citations
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a cutting-edge genome editing tool based on the adaptive immune mechanism of prokaryotes. This system, which operates through three key stages‒adaptation, expression, and interference‒offers high precision and efficiency in genetic modification. This article explores the mechanisms of CRISPR/Cas action and its applications in hematologic malignancies, breast cancer, colorectal cancer, gastric cancer, and lung cancer. Genome editing has demonstrated significant effectiveness in suppressing tumor growth, enhancing cellular sensitivity to therapy, and developing personalized treatment approaches. CRISPR/Cas enhances the efficacy of Chimeric Antigen Receptor T-cell Therapy (CAR-T) and helps overcome tumor cell resistance to treatment. The technology is also actively utilized in genetic screening to identify gene functions and discover new therapeutic targets. However, several challenges remain, including off-target effects, immune responses, and difficulties in delivering CRISPR components to target cells. This article discusses promising strategies to overcome these limitations, such as the development of novel Cas protein variants, improved delivery methods, and epigenetic approaches. CRISPR/Cas represents one of the most promising tools in molecular biology, providing the ability to precisely investigate gene functions and to develop new experimental strategies for therapeutic intervention. The potential of this technology is defined by its flexibility and applicability across a wide range of tasks‒including target validation, disease modeling, and the generation of advanced cellular products. However, its full integration into clinical practice requires further studies aimed at improving safety, reducing the frequency of unintended effects, and developing reliable delivery systems.
M. Omarov, E. Karacheva, M. M. Arapieva et al.· Сибирский научный медицински...· 0 citations
Recent advances in the application of CRISPR/Cas gene editing technology to enhance the antitumor activity of CAR-T cells against solid tumors are summarized and the key challenges currently faced are discussed.
Wenjing Liu, Jiayi Gu, Chenghao Xie et al.· Frontiers in Immunology· 0 citations
Small cell lung cancer (SCLC) is an aggressive and immunologically "cold" malignancy characterized by profound immunosuppression and limited responsiveness to immunotherapy. Its tumor immune microenvironment (TIME) exhibits defective antigen presentation, suppressive cytokine signaling, and abnormal stromal-metabolic interactions that collectively restrict immune activation and promote tumor progression. Overcoming this immune-cold state is an urgent prerequisite for improving therapeutic efficacy and achieving durable responses in SCLC.Converting SCLC from an immune-cold to an immune-active state requires integrated therapeutic strategies that relieve immunosuppression, restore antigen presentation, enhance effector lymphocyte infiltration and function, and overcome metabolic and stromal barriers that shape the suppressive TIME. This review integrates mechanistic insights with emerging therapeutic strategies for remodeling the SCLC TIME, focusing on radiotherapy, immunomodulatory therapies, stromal-targeted therapies, epigenetic therapy, and engineered immunotherapy platforms such as delta-like ligand 3 (DLL3)-directed bispecific T-cell engagers, CAR-T and cytokine-armored cells, biological vector-based immunotherapies, and nano-immunotherapy platforms. These advances outline a translational framework for converting immune-cold SCLC into an immune-responsive disease and achieving durable immunotherapeutic efficacy.
Zhuoyan Han, Jie Tong, Ya-Ling Feng et al.· Biochemical Pharmacology· 0 citations
This review summarizes recent progress in applying CRISPR systems in vivo for cancer immunotherapy, focusing on approaches that target cancer cells and the tumor microenvironment, as well as those that directly engineer immune cell populations themselves.
Cole W. Christopher, Xiaoyu Zhou· Frontiers in Immunology· 0 citations
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