Transfer Learning-Based Hyperspectral Image Classification Using Residual Dense Connection Networks.

The extraction of effective classification features from high-dimensional hyperspectral images, impeded by the scarcity of labeled samples and uneven sample distribution, represents a formidable challenge within hyperspectral image classification. Traditional few-shot learning methods confront the dual dilemma of limited annotated samples and the necessity for deeper, more effective features from complex hyperspectral data, often resulting in suboptimal outcomes. The prohibitive cost of sample annotation further exacerbates the challenge, making it difficult to rely on a scant number of annotated samples for effective feature extraction. Prevailing high-accuracy algorithms require abundant annotated samples and falter in deriving deep, discriminative features from limited data, compromising classification performance for complex substances. This paper advocates for an integration of advanced spectral-spatial feature extraction with meta-transfer learning to address the classification of hyperspectral signals amidst insufficient labeled samples. Initially trained on a source domain dataset with ample labels, the model undergoes transference to a target domain with minimal samples, utilizing dense connection blocks and tree-dimensional convolutional residual connections to enhance feature extraction and maximize spatial and spectral information retrieval. This approach, validated on three diverse hyperspectral datasets-IP, UP, and Salinas-significantly surpasses existing classification algorithms and small-sample techniques in accuracy, demonstrating its applicability to high-dimensional signal classification under label constraints.

Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.

BACKGROUND: Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. MAIN BODY: Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. CONCLUSION: OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

Correction to: The old CEACAMs find their new role in tumor immunotherapy.

Correction is needed to the original version of this article.

The old CEACAMs find their new role in tumor immunotherapy.

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) contain 12 family members(CEACAM1、CEACAM3、CEACAM4、CEACAM5、CEACAM6、CEACAM7、CEACAM8、CEACAM16、CEACAM18、CEACAM19、CEACAM20 and CEACAM21)and are expressed diversely in different normal and tumor tissues. CEA (CEACAM5) has been used as a tumor biomarker since 1965. Here we review the latest research and development of the structures, expression, and function of CEACAMs in normal and tumor tissues, and their application in the tumor diagnosis, prognosis, and treatment. We focus on recent clinical studies of CEA targeted cancer immunotherapies, including bispecific antibody (BsAb) for radio-immuno-therapy and imaging, bispecific T cell engager (BiTE) and chimeric antigen receptor T cells (CAR-T). We summarize the promising clinical relevance and challenges of these approaches and give perspective view for future research. This review has important implications in understanding the diversified biology of CEACAMs in normal and tumor tissues, and their new role in tumor immunotherapy.

Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses.

BACKGROUND: Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. METHODS: Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy. RESULTS: Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection. CONCLUSIONS: Our findings have important implication to HSV biology, infection, immunity and oHSVs.

The Tumorigenic Effect of Sphingosine Kinase 1 and Its Potential Therapeutic Target.

Sphingosine kinase 1 (SPHK1) regulates cell proliferation and survival by converting sphingosine to the signaling mediator sphingosine 1-phosphate (S1P). SPHK1 is widely overexpressed in most cancers, promoting tumor progression and is associated with clinical prognosis. Numerous studies have explored SPHK1 as a promising target for cancer therapy. However, due to insufficient knowledge of SPHK1 oncogenic mechanisms, its inhibitors' therapeutic potential in preventing and treating cancer still needs further investigation. In this review, we summarized the metabolic balance regulated by the SPHK1/S1P signaling pathway and highlighted the oncogenic mechanisms of SPHK1 via the upregulation of autophagy, proliferation, and survival, migration, angiogenesis and inflammation, and inhibition of apoptosis. Drug candidates targeting SPHK1 were also discussed at the end. This review provides new insights into the oncogenic effect of SPHK1 and sheds light on the future direction for targeting SPHK1 as cancer therapy.

The Emerging Roles of CIB1 in Cancer.

Calcium and integrin-binding protein 1 (CIB1) is an EF-hand calcium binding protein, which is involved in many cellular processes, including calcium signaling, cell survival and proliferation, cell migration, cell adhesion and apoptosis. A number of studies have found that CIB1 is ubiquitously expressed and is related to various human diseases, such as cancer, Alzheimer's disease (AD), cardiac hypertrophy and male infertility. The mechanism of CIB1 in human diseases is still not clear, although multiple functions of CIB1 are modulated by interacting with numerous interacting partners. As a calcium binding protein, the roles of CIB1 in calcium signaling by binding calcium or modulating some key modulators, such as calcineurin, integrin, inositol 1,4,5-trisphosphate receptor (IP3R) and taste 1 receptor member 2 (TAS1R2). The tumor promoting mechanisms of CIB1 have been described in different aspects, including promoting tumor cell cycle and proliferation, inhibiting tumor cell apoptosis, and mediating tumor cell migration and angiogenesis. In addition, multiple functions of CIB1, such as neural development, taste or gustation functions, and virus infection are also elucidated. These recent advances have significantly expanded our understanding of the knowledge of CIB1 and highlighted the potential mechanisms of CIB1 in tumor progression.

Involvement of Bim in Photofrin-mediated photodynamically induced apoptosis.

BACKGROUND/AIMS: Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells. METHODS: The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi. RESULTS: BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim. CONCLUSION: We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers.

Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta-analysis.

This study examined the effects of perioperative dexmedetomidine treatment on physiological modulators of surgical stress response. The quality of the included studies was assessed prior to performing meta-analyses of the weighted mean differences in the changes from baseline of stress hormones and interpreted in the light of statistical heterogeneity between the studies. Nineteen studies (844 surgical subjects) data were used for this meta-analysis. Dexmedetomidine administration significantly decreased blood cortisol levels (µg/dL) postoperatively (mean difference with 95% confidence interval (CI) from controls: -18.78 (-28.45, -9.10); P < 0.05). In the subgroup analysis, the mean difference between dexmedetomidine-treated and saline-treated subjects in the changes from baseline of the cortisol levels was -20.10 (-30.96, -9.25; P < 0.05) but, between dexmedetomidine- and comparator-treated subjects, it was not statistically significantly different (-15.13 (-49.78, 19.52); P < 0.05). Compared with controls, dexmedetomidine treatment also decreased adrenaline and noradrenaline levels significantly (mean difference in the percent changes from baseline: -90.41 (-145.79, -35.03)%; P < 0.05 and -62.82 (-85.47, -0.40.17)%; P < 0.05, respectively). Dexmedetomidine also decreased prolactin levels with a mean difference of -19.42 (-39.37, 0.52) µg/L (P = 0.06). In conclusion, perioperative use of dexmedetomidine reduces serum catecholamine and cortisol levels but the decrease in cortisol levels was not statistically different from the comparator anaesthetics. More data will be required to assess the effects of dexmedetomidine on corticotropin, prolactin, and growth hormone.

Ferroptosis: a promising target for fumarate hydratase-deficient tumor therapeutics literature review.

Background and Objective: This review aims to investigate the ferroptosis mechanism of fumarate hydratase (FH)-related tumors for the purpose of possible treatment of tumors. Ferroptosis is an iron (Fe)-dependent form of regulated cell death caused by lipid peroxidation on the cell membrane. Studies have implicated FH in tumorigenesis. As mutations in the FH gene alter cellular metabolism and increase tumorigenesis risk, particularly in the kidneys. As most tumor cells require higher amounts of ferrous ions (Fe2+) than normal cells, they are more susceptible to ferroptosis. Recent studies have indicated that ferroptosis is inhibited the pathogenesis and progression of FH-deficient tumors by regulating lipid and iron metabolism, glutathione-glutathione peroxidase 4 (GSH-GPX4), nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathways. While the Fe2+ content is significantly lower in FH-deficient tumor cells, than that in normal cells. It is promising to promote ferroptosis by increasing the concentration of Fe2+ in cells to achieve the purpose of tumor treatment. Methods: In this study, we searched for relevant articles on ferroptosis and FH-deficient tumors using PubMed database. Key Content and Findings: FH is a tumor suppressor. A number of basic studies have shown that the loss of FH plays an important role in hereditary leiomyomas and tumors such as renal cell carcinoma, ovarian cancer, and other tumors. This type of tumor cells can through induce ferroptosis, inhibit proliferation, migration and invasion of tumor cells, increase the sensitivity of tumor cells to chemotherapy, and reverse the drug resistance through various molecular mechanisms. At present, the research on ferroptosis in FH-related tumors is still in the basic experimental stage. Conclusions: This article reviews the anti-tumor effects and mechanisms of FH and ferroptosis, in order to further explore the medical value of ferroptosis in FH-related tumor therapy.

Inhibition of SPARC signal by aerobic exercise to ameliorate atherosclerosis.

BACKGROUND AND AIMS: Inflammation and atherosclerosis (AS) are closely associated to Secreted Protein Acidic and Rich in Cysteine (SPARC) and its related factors. This study attempted to define the role and the potential mechanism of SPARC and its related factors in ameliorating hyperlipidemia and AS by aerobic exercise intervention. METHODS: The AS rat model was established with a high-fat diet plus vitamin D3 intraperitoneal injection. Treadmill exercises training (5 days/week at 14 m/min for 60 min/day) for 6 weeks was carried out for AS rat intervention method. Western blotting and qRT-PCR were used to analyze the mRNA and protein expression of SPARC and its related factors, respectively. H&E staining was applied to evaluate the morphological changes and inflammation damage. Von Kossa staining was used to measure the degree of vascular calcification. Fluorescence immunohistochemistry staining was used to detect the expression and distribution of SPARC signal molecules. RESULTS: SPARC was highly expressed and co-localization with the smooth muscle marker α-SMC in the AS rat. And its downstream factors, NF-κB, Caspase-1, IL-1ß and IL-18 were upregulated (P < 0.05 or P < 0.01), FNDC5 expression was downregulated in AS rat model. However, slight declined body weight, delayed AS progression, decreased hyperlipidemia and favorable morphology of skeletal muscle and blood vessels have been detected in AS rat with aerobic exercise intervention. Moreover, the expression of SPARC and its downstream factors were decreased (P < 0.05 or P < 0.01), while elevated the expression of FNDC5 (P < 0.01) was observed after aerobic exercise intervention. CONCLUSIONS: This study suggested that aerobic exercise ameliorated hyperlipidemia and AS by effectively inhibiting SPARC signal, and vascular smooth muscle cells may contribute greatly to the protection of AS.

An enzyme activated fluorescent probe for LTA4H activity sensing and its application in cancer screening.

Early diagnosis of cancer is an efficient strategy to prevent tumor progression and improve the survival rate of patients. However, to discovery of reliable tumor-specific biomarkers remains a great challenge. Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc metalloenzyme with epoxide hydrolase activity and aminopeptidase activity, which plays important roles in allergic and inflammatory reactions and showed strong relevance with carcinoma progression. We thus sought to investigate the possibility of application LTA4H activity detection in cancer diagnosis. To achieve this, we herein develop an enzyme activated fluorescent probe for LTA4H activity sensing by incorporating the specific recognition unit of LTA4H with a red-emitting fluorophore. The acquired probe (named as ADMAB) showed high sensitivity and specificity toward LTA4H in vitro. By further application of ADMAB in living cells, significantly elevated LTA4H activity in cancer cell lines was observed when compared with normal cell lines and in vivo tracing A549 tumor in nude mice was also realized by ADMAB. Meanwhile, the wound-healing assay further revealed the importance of LTA4H in tumor metastasis. Moreover, the LTA4H activity in human serum sample was successfully detected by ADMAB and significantly elevated LTA4H activity in patients diagnosed with cancer was firstly found, which demonstrated ADMAB to be a useful tool for cancer diagnosis and LTA4H related biological study.

A pathway from JNK through decreased ERK and Akt activities for FOXO3a nuclear translocation in response to UV irradiation.

Forkhead box O (FOXO) transcription factors play an important role in physiological and pathological processes. Extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) can phosphorylate FOXO and cause its degradation or cytoplasmic retention, respectively, leading to tumorigenesis. In addition, C-Jun N-terminal protein kinase (JNK) can promote FOXO nuclear localization, leading to apoptosis. Using confocal imaging of cells transfected with GFP-FOXO3a, we visualized the dynamic translocation of GFP-FOXO3a from the cytoplasm to the nucleus after UV irradiation in a time- and dose-dependent manner. We also found that UV irradiation caused activation of JNK, which in turn inactivated ERK and Akt, leading to FOXO3a translocation and Bim expression. Our results indicate that nuclear translocation of FOXO3a can be regulated by UV irradiation through the JNK-ERK/Akt pathway.

Aerobic exercise alleviates pyroptosis-related diseases by regulating NLRP3 inflammasome.

Pyroptosis plays a crucial role in a variety of human diseases, including atherosclerosis, obesity, diabetes, depression, and Alzheimer's disease, which usually release pyroptosis-related cytokines due to inflammation. Many studies have demonstrated that aerobic exercise is a good option for decreasing the release of pyroptosis-related cytokines. However, the molecular mechanisms of aerobic exercise on pyroptosis-related diseases remain unknown. In this review, the effects of aerobic exercise on pyroptosis in endothelial cells, adipocytes and hippocampal cells, and their potential mechanisms are summarized. In endothelial cells, aerobic exercise could inhibit NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis by improving the endothelial function, while reducing vascular inflammation and oxidative stress. In adipocytes, aerobic exercise has been shown to inhibit pyroptosis by ameliorating inflammation and insulin resistance. Moreover, aerobic exercise could restrict pyroptosis by attenuating microglial activation, neuroinflammation, and amyloid-beta deposition in hippocampal cells. In summary, aerobic exercise alleviates the pyroptosis-related diseases by regulating the NLRP3 inflammation si0067naling.

The effect of tai chi intervention on NLRP3 and its related antiviral inflammatory factors in the serum of patients with pre-diabetes.

Background: NLRP3 inflammasome and its related antiviral inflammatory factors have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, but its contribution to pre-diabetes remains poorly understood. Objective: To investigate the effects and the potential mechanism of Tai Chi intervention on NLRP3 inflammasome and its related inflammatory factors in the serum of middle-aged and older people with pre-diabetes mellitus (PDM). Methods: 40 pre-diabetic subjects were divided into a pre-diabetic control group (PDM-C group, N=20) and a Tai Chi group (PDM-TC group, N=20) by random number table. 10 normoglycemic subjects (NG) were selected as controls. We measured clinical metabolic parameters and collected blood samples before and after the 12 weeks of Tai Chi intervention. Antiviral inflammatory factors in serum were detected by enzyme-linked immunosorbent assay. Results: The blood glucose, insulin resistance, and inflammation in PDM groups were higher than those in the NG group (P<0.05 and P<0.01, respectively). The results also suggested that 12 weeks of Tai Chi intervention could reduce body weight, blood pressure, blood glucose, insulin resistance, blood lipid, and the expressions of serum inflammatory factors in the pre-diabetic population. Conclusion: Tai Chi intervention may improve blood glucose, lipid levels, and insulin resistance in middle-aged and elderly pre-diabetic patients by reducing the level of NLRP3 inflammasome and its related inflammatory factors.

Challenges of phototherapy for neonatal hyperbilirubinemia (Review).

Phototherapy is universally recognized as the first option for treating neonatal jaundice due to its unparalleled efficiency and safety in reducing the high serum free bilirubin levels and limiting its neurotoxic effects. However, several studies have suggested that phototherapy may elicit a series of short- and long-term adverse reactions associated with pediatric diseases, including hemolysis, allergic diseases, DNA damage or even cancer. The aim of the present review was to summarize the etiology, mechanism, associated risks and therapeutic strategies for reducing high neonatal serum bilirubin levels. In order to shed light on the negative effects of phototherapy and to encourage implementation of a reasonable and standardized phototherapy scheme in the clinic, the present review sought to highlight the current understanding of the adverse reactions of phototherapy, as it is necessary to further study the mechanism underlying the development of the adverse effects of phototherapy in infants in order to explore novel therapeutic alternatives.

DNA barcode to trace the development and differentiation of cord blood stem cells (Review).

Umbilical cord blood transplantation was first reported in 1980. Since then, additional research has indicated that umbilical cord blood stem cells (UCBSCs) have various advantages, such as multi­lineage differentiation potential and potent renewal activity, which may be induced to promote their differentiation into a variety of seed cells for tissue engineering and the treatment of clinical and metabolic diseases. Recent studies suggested that UCBSCs are able to differentiate into nerve cells, chondrocytes, hepatocyte­like cells, fat cells and osteoblasts. The culture of UCBSCs has developed from feeder­layer to feeder­free culture systems. The classical techniques of cell labeling and tracing by gene transfection and fluorescent dye and nucleic acid analogs have evolved to DNA barcode technology mediated by transposon/retrovirus, cyclization recombination­recombinase and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR­associated protein 9 strategies. DNA barcoding for cell development tracing has advanced to include single cells and single nucleic acid mutations. In the present study, the latest research findings on the development and differentiation, culture techniques and labeling and tracing of UCBSCs are reviewed. The present study may increase the current understanding of UCBSC biology and its clinical applications.

Cell­cell fusion as an important mechanism of tumor metastasis (Review).

Cell­cell fusion is a dynamic biological phenomenon, which plays an important role in various physiological processes, such as tissue regeneration. Similarly, normal cells, particularly bone marrow­derived cells (BMDCs), may attempt to fuse with cancer cells to rescue them. The rescue may fail, but the fused cells end up gaining the motility traits of BMDCs and become metastatic due to the resulting genomic instability. In fact, cell­cell fusion was demonstrated to occur in vivo in cancer and was revealed to promote tumor metastasis. However, its existence and role may be underestimated, and has not been widely acknowledged. In the present review, the milestones in cell fusion research were highlighted, the evidence for cell­cell fusion in vitro and in vivo in cancer was evaluated, and the current understanding of the molecular mechanisms by which cell­cell fusion occurs was summarized, to emphasize their important role in tumor metastasis. The summary provided in the present review may promote further study into this process and result in novel discoveries of strategies for future treatment of tumor metastasis.

Could gastrointestinal tumor-initiating cells originate from cell-cell fusion in vivo?

Tumor-initiating cells (TICs) or cancer stem cells are believed to be responsible for gastrointestinal tumor initiation, progression, metastasis, and drug resistance. It is hypothesized that gastrointestinal TICs (giTICs) might originate from cell-cell fusion. Here, we systemically evaluate the evidence that supports or opposes the hypothesis of giTIC generation from cell-cell fusion both in vitro and in vivo. We review giTICs that are capable of initiating tumors in vivo with 5000 or fewer in vivo fused cells. Under this restriction, there is currently little evidence demonstrating that giTICs originate from cell-cell fusion in vivo. However, there are many reports showing that tumor generation in vitro occurs with more than 5000 fused cells. In addition, the mechanisms of giTIC generation via cell-cell fusion are poorly understood, and thus, we propose its potential mechanisms of action. We suggest that future research should focus on giTIC origination from cell-cell fusion in vivo, isolation or enrichment of giTICs that have tumor-initiating capabilities with 5000 or less in vivo fused cells, and further clarification of the underlying mechanisms. Our review of the current advances in our understanding of giTIC origination from cell-cell fusion may have significant implications for the understanding of carcinogenesis and future cancer therapeutic strategies targeting giTICs.

Bispecific T cell engagers and their synergistic tumor immunotherapy with oncolytic viruses.

Tumor immunotherapy, especially T cell based therapy, is becoming the main force in clinical tumor therapies. Bispecific T cell engager (BiTE) uses the single chain variable fragments (scFv) of two antibodies to redirect T cells to kill target cells. BiTEs for hematologic tumors has been approved for clinical use, and BiTEs for solid tumors showed therapeutic effects in clinical trials. Oncolytic viruses (OVs) of the adenovirus expressing p53 and herpes simplex virus expressing GM-CSF was approved for clinical use in 2003 and 2015, respectively, while other OVs showed therapeutic effects in clinical trials. However, BiTE and Oncolytic virus (OV) have their own limitations. We propose that OV-BiTE has a synergistic effect on tumor immunotherapy. Feng Yu et al. designed the first OV-BiTE in 2014, which remarkably eradicated tumors in mice. Here we review the latest development of the structure, function, preclinical studies and/or clinical trials of BiTE and OV-BiTE and provide perspective views for optimizing the design of OV-BiTE. There is no doubt that OV-BiTE is becoming an exciting new platform for tumor immunotherapy and will enter clinical trial soon. Exploring the therapeutic effects and safety of OV-BiTE for synergistic tumor immunotherapy will bring new hope to tumor patients.