Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments

Li, Xudong; Li, Wei; Xu, Linping; Song, Yongping

doi:10.1097/cm9.0000000000002818

Cited by 7 publications

(1 citation statement)

References 146 publications

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“…The advantages of CAR-M cells include a wide range of sources, phagocytosis, greater ability to infiltrate, and better resistance to TME inhibition. 14 , 66 , 67 However, the development of CAR-M cell-related technologies is currently less mature compared to CAR-T and CAR-NK cells. The current research on CAR-NK cell therapy and CAR-M cell therapy for solid tumor treatment is still in its nascent stages.…”

Section: Discussionmentioning

confidence: 99%

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Miao,

Zhang,

et al. 2024

Human Vaccines & Immunotherapeutics

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CAR-T cell therapy has emerged as a significant approach for the management of hematological malignancies. Over the past few years, the utilization of CAR-T cells in the investigation and treatment of solid tumors has gained momentum, thereby establishing itself as a prominent area of research. This descriptive study involved the retrieval of articles about CAR-T cell therapy for solid tumors from the Web of Science Core Collection (WoSCC) database. Subsequently, bibliometric analysis and knowledge map analysis were conducted on these articles. The field under consideration is currently experiencing a period of swift advancement, as evidenced by the escalating number of publications in this domain each year. The United States holds an indisputable position as the foremost leader in this particular field, with the University of Pennsylvania emerging as the most active institution. The authors with the highest citation frequency and co-citation frequency are Carl H. June and Shannon L. Maude, respectively. The research hotspots in this field mainly focus on five aspects. Additionally, 10 emerging themes were identified. This study undertakes a comprehensive, systematic, and objective analysis and exploration of the field of CAR-T cell treatment for solid tumors, utilizing bibliometric methods. The findings of this study are expected to serve as a valuable reference and enlightenment for future research endeavors in this particular domain.

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Section: Discussionmentioning

confidence: 99%

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Miao,

Zhang,

et al. 2024

Human Vaccines & Immunotherapeutics

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Novel immunotherapeutic approaches in gastric cancer

Yang,

Lin,

Huang

et al. 2024

Precision Clinical Medicine

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Gastric cancer is a malignant tumor that ranks third in cancer-related deaths worldwide. Early-stage gastric cancer can often be effectively managed through surgical resection. However, the majority of cases are diagnosed in advanced stages, where outcomes with conventional radiotherapy and chemotherapy remain unsatisfactory. Immunotherapy offers a novel approach to treating molecularly heterogeneous gastric cancer by modifying the immunosuppressive tumor microenvironment. Immune checkpoint inhibitors and adoptive cell therapy are regarded as the promising modalities in cancer immunotherapy. FDA-approved PD1 inhibitors, such as Pembrolizumab, in combination with chemotherapy, have significantly extended overall survival in gastric cancer patients and is recommended as a first-line treatment. Despite challenges in solid tumor applications, adoptive cell therapy has demonstrated efficacy against various targets in gastric cancer treatment. Among these approaches, CAR-T cell therapy research is the most widely explored and CAR-T therapy targeting claudin18.2 has shown acceptable safety and robust anti-tumor capabilities. However, these advancements primarily remain in preclinical stages, and further investigation should be made to promote their clinical application. This review summarizes the latest research on immune checkpoint inhibitors and adoptive cell therapy and their limitations, as well as the role of nanoparticles in enhancing immunotherapy.

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Development of a novel HER2-CAR monocyte cell therapy with controllable proliferation and enhanced anti-tumor efficacy

Yang,

Wang,

Wei

et al. 2024

Chinese Medical Journal

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Background: One of the significant challenges for cell therapies, such as chimeric antigen receptor (CAR)-T cell therapy, is the poor infiltration of immune cells into tumor tissues. CAR-monocytes/macrophages (CAR-M) are promising therapies because of their enrichment in the tumor microenvironment. Thus, we constructed a novel CAR-M to facilitate the infiltration of T cells and other immune cells. Methods: The suicide gene inducible caspase-9 (iCasp9) and anti-erb-b2 receptor tyrosine kinase 2 (HER2) CAR elements were transfected into THP1 (an immortalized human monocyte cell line) by lentivirus. The suicide efficiency and specific anti-tumor efficacy were assessed using flow cytometry, inCucyte, and tumor-bearing BALB/c-nude mouse models. The activation of related signaling pathways in CAR-THP1 activation was explored by transcriptome sequencing. Finally, the synergistic therapeutic efficacy of CAR-THP1 combined with RAK cell treatment was demonstrated in tumor-bearing NOD.CB17-Prkdcscid Il2rgtm1/Bcgen mouse models. Results: We developed a novel CAR-THP1 which incorporated iCasp9, CD3ζ and CD147 intracellular segments, based on the first-generation HER2-CAR backbone. By constructing and comparing a series of CARs with different permutations, CAR-CD3ζ-CD147-iCasp9-THP1 was selected as the optimal combination. CAR-CD3ζ-CD147-iCasp9-THP1 initiated suicide quickly and efficiently under the control of iCasp9 gene, which enabled us to achieve controlled proliferation of CAR-THP1. CAR-THP1 also exhibited robust specific anti-tumor efficacy independently of T cells in vitro and in vivo. Through transcriptional sequencing, we found that CAR-THP1 tended to differentiate into the M1 phenotype and bridged innate and adaptive immunity. A combination of CAR-THP1 and Retronectin actived killer cells (RAKs) showed better therapeutic efficiency, as the metalloproteinases (MMPs) secreted by CAR-THP1 facilitated the degradation of the dense tumor matrix. This further assisted intratumoral infiltration of T cells and augmented the anti-tumor immune response. Conclusion: CAR-THP1 might be effective against HER2-positive tumor cells and has great potential for combination therapy with other immune cells.

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Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments

Cited by 7 publications

References 146 publications

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012–2023)

Novel immunotherapeutic approaches in gastric cancer

Development of a novel HER2-CAR monocyte cell therapy with controllable proliferation and enhanced anti-tumor efficacy

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