Due to the success of chimeric antigen receptors (CARs) in hematological tumors, CARs are also being studied to treat solid tumors. Improving the ability of CARs to penetrate solid tumor tissues is one of the biggest challenges. As the most malignant cancer of the female reproductive system, the survival rate of ovarian cancer has not been significantly improved by traditional therapy methods; therefore, it is necessary to develop new therapeutic targets and new immunotherapy methods for ovarian cancer. UPAR is a glysocylphosphatidylinositol (GPI) anchoring membrane protein that is differentially expressed in normal tissues and ovarian cancer tissues. It has been shown that uPAR up-regulation promotes tumor development, proliferation, invasion, and metastasis, and uPAR is also up-regulated in tumor matrix components. In our study, CARs were designed using the natural ligand binding fragment of uPAR for ovarian cancer.

Background: Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus’s development.Case presentation: A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient’s anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing.Conclusions: Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists.

Background: NK cells are a class of innate lymphocytes capable of nonspecifically killing tumor cells without MHC restriction or prior sensitization. Recent advancements in biotechnology, particularly the development of chimeric antigen receptors (CAR) and related technologies, have enabled targeted tumor cell elimination. CAR endows NK cells with enhanced functionality, with the extracellular domains typically consisting of single‐chain variable fragments (scFv) for targeting specific antigens. CAR‐NK cells have shown excellent results in several preclinical studies and clinical trials for hematologic malignancies. However, their clinical application in the treatment of solid tumors is still insufficient. Current treatments for gynecological cancers primarily involve surgery, chemotherapy, and radiotherapy, all of which often present substantial side effects and variable efficacy. While CAR‐T cell therapy has shown effectiveness in certain gynecological tumors, its clinical application is hindered by severe side effects, such as Cytokine Release Syndrome (CRS) and Graft‐Versus‐Host Disease (GVHD). CAR‐NK cell therapy offers improved safety profiles in clinical applications.Objective: This review aims to systematically evaluate recent methodological innovations in CAR‐NK engineering and their translational potential in tumor‐targeted treatment, providing valuable insights for clinical trials and studies.Methods: Electronic databases, including PubMed and Web of Science were searched for relevant literature. Keywords are as follows: CAR‐NK cell; Chimeric antigen receptor; Solid tumor; cell therapy; gynecological cancers.Results: CAR‐NK engineering has innovations such as multi‐targeted CAR design, gene editing for enhanced persistence, and “off‐the‐shelf” CAR‐NK cells compared to CAR‐T cells.Conclusion: CAR‐NK cell therapy combines safety and anti‐tumor efficacy, particularly for gynecological cancers.

Ovarian Cancer (OC), the deadliest gynecological malignancy, poses a major therapeutic challenge in advanced stages owing to its high recurrence rate and metastatic potential. In this regard, it is noteworthy that immunotherapy has recently gained significant attention in OC treatment, a phenomenon attributable to notable advances in over‐the‐counter Chimeric Antigen Receptor (CAR)‐based cell therapy. At the heart of CAR‐T Cell (CAR‐T) immunotherapy is genetically modified CAR molecules that enable immune cells to target and recognize tumor antigens. Based on such strategies, CAR‐T therapies have developed rapidly in hematological oncology and are gradually being extended to solid tumors. Despite their potential in OC treatment, several factors, including off‐target effects attributable to the lack of Tumor‐Specific Antigens (TSAs), as well as severe side effects such as tumor immune barriers, Cytokine Release Syndrome (CRS), and neurotoxicity, have been established to limit the clinical use of CAR‐T therapies. Moreover, compared to CAR‐T, CAR‐Natural Killer (NK) and CAR‐Macrophage (M) therapies have distinct advantages. The killing mechanism of NK cells integrates both CAR‐dependent and non‐dependent pathways, avoiding severe CRS and neurotoxicity. Furthermore, besides directly phagocytosing tumors due to its strong ability to infiltrate tumors, CAR‐M therapy could also effectively improve the Immunosuppressive Microenvironment (IME) via immunomodulatory factor secretion to remodel M2‐type Tumor‐Associated Macrophages (TAMs) into the M1 phenotype with anti‐tumor function. In this review, we systematically describe the research progress in CAR‐T therapy for OC and compare the similarities and differences of three types of cellular therapies (CAR‐T, CAR‐NK, and CAR‐M) regarding their mechanisms of action, clinical advantages, and technological bottlenecks. We hope that our findings will provide a theoretical basis for optimizing immunotherapeutic strategies for OC. Trial Registration: ClinicalTrials.gov identifier: NCT03585764

NK cells are an innate class of lymphocytes in the human body that can achieve non-specific killing of tumor cells without MHC restriction or prior sensitization. In recent years, targeted killing of tumor cells has become possible due to the development of diverse biological technology, particularly the chemical chimeric antigen receptors (CAR), and other technologies. CAR gives NK cells a new magic, and its extracellular domains of the recognition region are usually single-chain antibodies (scFv), which can be targeted to specific antigens. CAR-NK cells have shown excellent results in several preclinical studies and clinical trials for hematologic malignancies. However, their clinical application in the treatment of solid tumors is still insufficient. Currently, the treatment of gynecological tumors relies mainly on surgery, chemotherapy, and radiotherapy, which are often accompanied by significant side effects and limited efficacy. CAR-T cell therapy has shown efficacy in certain gynecological tumors. However, side effects that are still urgent problems in clinical applications such as Graft-Versus-Host Disease (GVHD) and Cytokine Release Syndrome (CRS) have been observed. In contrast, CAR-NK cell therapy shows potential advantages in this area. Based on the above, this review mainly focuses on the development of CAR-NK cell constructs and their promising applications for immunotherapy of gynecological malignancies, aiming to provide references for clinical trials and clinical studies.

Ovarian cancer (OC) is characterised by high malignancy. Tumour immune microenvironment (TME) may serve as a breakthrough for therapy. Chemokines are responsible for the recruitment of diverse immune cells in TME. We identify the association between chemokines and T and NK cells. This study was conducted to screen the chemokine derived from T and NK cells in OC single‐cell RNA sequencing (scRNA‐seq) dataset was acquired from the GEO database. Total 64 genes were collected. The intersection of marker genes of T and NK cells and chemokine‐related genes was considered as key chemokine‐related genes. Then, cell‐cell communication analysis, pseudotime analysis and transcription factors (TFs)–target genes regulatory network construction, were performed. Immunohistochemical staining experiments and wound healing assays are performed. The results found 21 distinct cell subgroups and 8 core cell types. Total 667 and 611 marker genes were identified in T and NK cells, respectively. Eight key chemokine‐related genes were found. Also, 49 TFs‐related to cell subtypes were obtained, and the TFs with the highest activation degree was SPI1. Eight key chemokine‐related genes were mainly distributed in T cells, NK cells and monocyte cells. The pseudotime trajectory shown that key chemokine‐related genes were highly expressed in T and NK cells in the later stage of differentiation. CCL5 exhibits differences in ovarian malignant tumour tissues compared with normal ovarian tissues. These findings provide novel insights for subsequent exploration in OC.