Search Results (587)

Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K–Akt–Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17–19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K–Akt inhibition and caspase-3–mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments. Full article

Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage “vicious cycle” of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of underappreciated cellular players in this metastatic takeover: megakaryocytes, erythroid lineage cells, and perivascular stromal subsets. Far from being passive bystanders, these cells actively shape the metastatic niche. For instance, megakaryocytes and platelets go beyond their role in transport; they orchestrate immune evasion and dormancy through mechanisms such as transforming growth factor-β1 (TGF-β1) signaling and the physical shielding of tumor cells. In parallel, we uncover a distinct “erythroid-immune” axis: here, stress-induced CD71⁺ erythroid progenitors suppress T-cell responses via arginase-mediated nutrient depletion and checkpoint engagement, forming a potent metabolic barrier against immune attack. Furthermore, leptin receptor–positive (LepR⁺) perivascular stromal cells emerge as key structural players. These stromal subsets not only act as anchoring points for DTCs but also maintain them in protective vascular zones via CXCL12 chemokine gradients. Altogether, these findings reveal that the metastatic bone marrow niche is not static; it is a highly dynamic, multi-lineage ecosystem. By mapping these intricate cellular interactions, we argue for a paradigm shift: targeting these early and cooperative crosstalk, whether through glycoprotein-A repetitions predominant (GARP) blockade, metabolic reprogramming, or other niche-disruptive strategies, could unlock new therapeutic avenues and prevent metastatic relapse at its root. Full article

Kynurenic acid (KYNA), a small molecule derived from the tryptophan–kynurenine pathway, can readily diffuse across biological membranes and act as an endogenous ligand for receptors such as the aryl hydrocarbon receptor (Ahr). While KYNA dysregulation is implicated in neurodegenerative disorders, the role of the KYNA–Ahr-IL-6 axis in MSC proliferation and differentiation remains poorly defined. We investigated the impact of KYNA on murine bone marrow-derived MSCs (BM-MSCs) at various concentrations (10–200 μM) and time points (8–48 h). The BM-MSC phenotype was assessed via flow cytometry; proliferation, via cell counting; and the gene expression of Ahr, Cyp1a1, Cyp1b1, and Il-6, via quantitative real-time PCR. Multipotency was evaluated through adipogenic, osteogenic, and chondrogenic differentiation assays with histochemical confirmation. KYNA significantly upregulated Ahr mRNA expression. Among the tested concentrations, 100 μM KYNA induced the highest Ahr expression (~19.1 ± 1.5-fold greater than that of the untreated controls, p < 0.005). Notably, 10 and 50 μM KYNA caused moderate induction, whereas compared with 100 μM KYNA, 200 μM did not further increase expression. In addition, KYN treatment increased Cyp1a1, Cyp1b1, and Il-6 expression, with increases of ~64.6 ± 4.5-fold, ~43.6 ± 2.3-fold, and ~41.6 ± 1.2-fold, respectively. Compared with no treatment, 100 µM KYNA enhanced BM-MSC proliferation by 1.210 ± 0.02, 1.189 ± 0.03, and 1.242 ± 0.02-fold across passages P3, P4, and P5, respectively (p < 0.05), without altering Sca-1, CD90, or CD45 expression or impairing trilineage differentiation potential. KYNA may activate the AHR–IL-6 signaling axis to promote BM-MSC expansion. This controlled proliferative effect, without loss of phenotypic or functional integrity, highlights the pharmacological potential of KYNA as a small-molecule modulator for stem cell-based therapies. Full article

Moringa oleifera, widely recognized as the horseradish tree or drumstick tree, is classified within the Moringaceae family, which comprises 13 species predominantly distributed across tropical and subtropical regions. The plant possesses a variety of therapeutic, nutritional, and beneficial health properties, including its potential to enhance the immune system. The present work provides extensive bibliographic research addressing the chemical composition of Moringa oleifera and its immunomodulatory properties with a focus on the cellular and molecular mechanisms involved in the regulation of immune function, which is crucial in unchecked cell proliferation and metastasis. The chemical composition of Moringa oleifera, including kaempferol, chlorogenic acid, quercetin, and niazimicin, varies between different biological parts of the plant (seeds, leaves, roots, and stems). The presence of these various chemical compounds contributes to the plant’s effect on the immune response via different pathways. Several studies indicate that Moringa oleifera mitigates inflammation by suppressing key pro-inflammatory mediators, such as TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE-2), and cyclooxygenase-2 (COX-2), while simultaneously enhancing anti-inflammatory mediators through activation of PPAR-γ. Furthermore, the immunomodulatory properties and possible application in health promotion and disease prevention, especially in cancer therapy, are discussed. Studies indicate that Moringa oleifera can modulate the tumor microenvironment (TME) by reducing Treg polarization, enhancing NK cell cytotoxicity, and prompting the proliferation and clonal expansion of CD8⁺ and CD4⁺ T lymphocytes. Together, Moringa oleifera could be considered for the treatment of conditions related to immune dysregulation, such as cancer. Full article

Background: The survival of newly diagnosed multiple myeloma (NDMM) has improved markedly worldwide with the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies. However, real-world progress among Chinese patients remains underexplored. This study evaluated 20-year survival trends in patients with NDMM treated in our institute and benchmarked them against outcomes from the Flatiron Health database in the United States. Patients and methods: Consecutive adults diagnosed with NDMM in our institute between 2003 and 2023 were retrospectively analyzed. U.S. patients were identified from the Flatiron Health database using similar inclusion criteria. Clinical characteristics, first-line regimens, and autologous stem cell transplantation (ASCT) rates were summarized. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier methods. Results: Among 1622 Chinese and 12,582 US patients, median age was 57 vs. 68 years. The median PFS and OS of NDMM patients in our institute was 40.1 months and 99.6 months, respectively. Induction therapy in the NICHE cohort changed markedly from primarily chemo-based therapy to combined PIs + IMIDs-based treatment, whereas these treatments were used much earlier in Flatiron. Uptake of new therapies in China increased rapidly after their inclusion in national health insurance. ASCT utilization was higher overall in China (34.9% vs. 22.1%) but remained lower among patients >65 years (6.7% vs. 12.1%). Conclusions: Two decades of real-world data from a major Chinese myeloma center demonstrate substantial improvements in survival and modernization of NDMM treatment, while highlighting persistent disparities amongst older adults. Full article

Triple Negative Breast Cancers (TNBCs) are heterogeneous and aggressive tumors with a median overall survival of less than two years. Despite the availability of new drugs, the prognosis remains poor, implicating a more aggressive clinical course in the metastatic setting. This study investigated the effects of metronomic treatment (mCHT) with 5-fluorouracil (5-FU) plus vinorelbine (VNR) on spheroids derived from two different TNBC cell lines (BT-549 and MDA-MB-231) and a patient-derived primary cell line (MS-186). mCHT significantly reduced spheroid growth and altered spheroid architecture, with a pronounced effect in second-generation spheroids, enriched in self-renewing cancer stem cells (CSCs). Expression of CSC-related markers (CD44, CD133, NOTCH-1, and MYC) was more significantly altered—both at the mRNA and protein levels—by mCHT than by standard treatment (STD). In MS-186-derived spheroids, mCHT downregulated EZH2 and STAT3, key regulators of CSC maintenance, and reduced H3K27ac, suggesting a global epigenetic reprogramming. Unlike STD, which partially and transiently reduced stemness markers, mCHT achieved sustained suppression, indicating preferential targeting of therapy-resistant CSCs. These results indicate mCHT as a promising strategy for specifically aiming at the CSC-like compartment in TNBC, underscoring a therapeutic approach that reprograms key epigenetic networks and overcomes resistance to treatment. Full article

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting—when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its wide application. To address this challenge, several alternative cell-based strategies have been developed. One of these is represented by cytokine-induced killer (CIK) cells, generated from donor peripheral blood mononuclear cells through stimulation with anti-CD3 antibodies, interferon-γ, and interleukin-2. These cells are characterized by a hybrid phenotype, combining T-cell functions with natural killer-like properties, and exhibit antitumor activity in an MHC-unrestricted manner. CIK cells are generally well tolerated and associated with low toxicity but their efficacy is so far modest. Based on the experience of CAR-T in the treatment of B-cell lymphoid disease, CIK cells have been engineered with chimeric antigen receptors (CAR) developing the CARCIK cells. This novel cellular strategy represents a promising approach in the treatment of acute myeloid and lymphoid leukemia relapsed post-allo-HSCT. This review provides an overview of the current CAR-CIK experiences in the setting of acute leukemias and outlines future directions for their clinical translation. Full article

Mesenchymal stem cells (MSCs) are pivotal in regenerative medicine due to their high differentiation potential and therapeutic versatility. MSCs are multipotent cells capable of differentiating into adipocytes, chondroblasts, osteoblasts, and, under specific conditions, neural, myocyte, and epidermal lineages. This cell type contributes to tissue repair, immunomodulation, and regenerative therapies for cardiac, orthopedic, and hematological disorders. Accurate identification and characterization of these stem cells are essential for both research and clinical applications. MSCs are typically defined by plastic adherence, expression of surface markers CD105, CD73, and CD90, low or absent expression of hematopoietic markers (CD45, CD34), and in vitro differentiation potential. Understanding the expression patterns and functional relevance of these surface markers is critical for improving isolation strategies, enhancing therapeutic efficacy, and minimizing adverse effects. This review provides a comprehensive overview of the principal surface markers of MSCs, highlighting their significance in stem cell biology and clinical translation. Full article

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country. Full article

Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHED) are a promising source for regenerative therapies due to their multipotency, proliferative capacity, and immunomodulatory properties. The present study aimed to isolate and characterize SHED subpopulations based on CD71 and CD146 expression and evaluate their multilineage differentiation potential. SHED were obtained from pediatric donors and separated into CD71⁺, CD71⁻, CD146⁺, and CD146⁻ fractions using magnetic-activated cell sorting (MACS). CD71⁺/CD71⁻ and CD146⁺/CD146⁻ populations were isolated independently; no simultaneous double sorting for both markers was performed. Immunocytochemistry was employed to confirm the expression of surface and intracellular markers, including STRO-1, CD44, nestin, and vimentin. Multilineage differentiation assays toward osteogenic, adipogenic, and chondrogenic lineages revealed that CD71⁺ cells exhibited reduced osteogenic capacity compared to CD71⁻ cells, whereas CD146⁺ cells showed enhanced osteogenic and adipogenic differentiation. Chondrogenic differentiation seemed unaffected by marker expression under the 2D conditions employed. These results highlight functional heterogeneity within SHED populations and indicate that CD71 and CD146 independently influence differentiation outcomes. The selective enrichment of CD146⁺ SHED may enhance osteogenic and adipogenic regenerative applications, while CD71⁺ subsets may serve as a valuable model for studying proliferation and paracrine effects. Limitations include the use of in vitro differentiation assays and the absence of in vivo validation; additionally, combined CD71/CD146 analysis may further clarify the relationship between metabolic activity and stem/progenitor niche characteristics. Overall, marker-based characterization of SHED subpopulations provides insight into their biological properties and potential utility in targeted cell-based therapeutic strategies. Full article

For patients with relapsed/refractory (R/R) follicular lymphoma (FL) after ≥2 prior lines of therapy, T-cell-redirecting therapies—including the bispecific CD3xCD20 antibody (BsAbs) mosunetuzumab (mosu) and chimeric antigen receptor T-cell (CAR-T) therapies such as axicabtagene ciloleucel (axi-cel), lisocabtagen maraleucel (liso-cel), and tisagenlecleucel (tisa-cel)—are approved by the FDA and EMA. Treatment selection should consider patient-related factors, prior therapeutic exposure, and toxicity profiles. We describe the 20-year history of a patient with R/R FL. At the fourth relapse, both BsAbs and CAR-T cells were available; however, due to the cumulative toxic burden and the high risk of cytopenias, mosu was selected as the preferred option. During mosu, the patient developed pure red cell aplasia unrelated to infections. Despite achieving a partial response after eight cycles of mosu, this complication led to the decision to proceed with allogeneic stem cell transplantation (allo-HSCT). The course was ultimately complicated by severe early toxicity with massive hemoptysis, acute respiratory failure, and hemorrhagic alveolitis, resulting in a fatal outcome. This case illustrates the delicate balance required in selecting between BsAbs and CAR-T therapy in R/R FL. Contributing factors to the patient’s fragility included profound immune status, transfusion-dependent red cell aplasia, prior cumulative chemotherapy, and pulmonary toxicity associated with conditioning regimens. The case underscores the importance of individualized treatment strategies and suggests that earlier integration of novel T-cell-redirecting therapies may mitigate cumulative toxicity and infection risk. Individualized therapeutic planning is critical in heavily pretreated R/R FL. In select cases, bridging strategies using BsAbs can provide disease control and facilitate transplantation. Still, careful assessment of patient fitness, marrow reserve, and cumulative toxicity is essential to minimize the risk of fatal complications. Full article

Osteoarthritis (OA) is a debilitating joint disease affecting over 500 million people globally, characterized by cartilage degradation, chronic pain, and failed tissue repair. Neurogenic inflammation, driven by neuropeptides including Substance P (SP) and calcitonin gene-related peptide (CGRP), plays a key role in the pathogenesis of OA. This study explores the therapeutic potential of extracellular vesicles (EVs) derived from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) transduced with CGRP antagonist CGRP_8-37 (aCGRP IFP-MSC EVs). These EVs are enriched in anti-inflammatory miRNAs and proteins, and they express neprilysin (CD10), enabling SP degradation. Herein, several LncRNAs were identified, which have been known to interact with miRNAs that affect the knee joint homeostasis. Specifically, 11 LncRNAs (ZFAS1, EMX2OS, HOTAIRM1, RPS6KA2-AS1, DANCR, LINC-ROR, GACAT1, GNAS-AS1, HAR1A, OIP5-AS1, TERC) interact with miRNAs that promote cell proliferation, prevent apoptosis, and preserve homeostasis. In vitro, aCGRP IFP-MSC EVs downregulated pro-inflammatory markers (TNF, TLR4, MAPK8) in dorsal root ganglia and promoted chondrocyte gene expression consistent with anabolism and matrix remodeling. In vivo, intra-articular EV delivery attenuated pain behaviors, preserved the cartilage structure, restored PRG4+ stem/progenitor cell localization, and trended toward reduced SP levels. Histological analysis confirmed improved collagen organization and reduced matrix degradation. These findings suggest that aCGRP IFP-MSC EVs exert multimodal effects on neuroinflammation, cartilage regeneration, and joint homeostasis. This cell-free, gene-enhanced EV therapy offers a promising disease-modifying strategy for the treatment of OA, with the potential to address both structural changes and chronic pain associated with this disease. Full article

Background: Severe dysfunction of the human limbus associated with limbal stem cell deficiency is a therapeutic challenge, especially when a structural alteration of the limbal niche is associated. Methods: We have evaluated seven decellularization protocols applied to 20 human sclero-corneal limbus, based on the use of SDS (protocol P1), SDS + NaCl (P2), SDS + triton X-100 + SDC + enzymatic treatment (P3), SDS + triton X-100 + SDC + enzymatic treatment + trypsin (P4), sulfobetains + DNAse (P5), sulfobetains + SDC + DNAse (P6) and SDC + DNAse (P7). The decellularization efficiency of each protocol, biocompatibility and safety, as well as their capability to support cell attachment and differentiation, were evaluated. Results: Results showed that the use of protocols P1 to P4, based on strong ionic detergents such as SDS, was not efficient for decellularizing the human limbus. Conversely, protocols P5, P6 and P7 removed more than 95% of DNA while preserving 60–100% of the extracellular matrix components. These protocols were biocompatible, as macrophages cultured with decellularized scaffolds were viable and differentiated to the pro-regenerative M2 phenotype (CD163/CD86 ratio > 2) without inducing a significant increase in reactive oxygen species (ROS). Protocols P6 and P7 supported cell attachment, survival and differentiation of corneal epithelial cells and four types of mesenchymal stem cells cultured on the surface of these scaffolds. Cellularized limbi showed positive expression of several limbal cell markers, especially in scaffolds decellularized with protocol P6. Conclusions: These results support the use of protocol P6 for the generation of human limbal substitutes by tissue engineering using decellularized human limbi. Future studies should determine the clinical potential of the regenerative biomaterial generated in patients with structural limbal damage, particularly in patients with chemical burns and aniridia, where conventional stem cell therapies fail. Full article

CD44 variant (CD44v) isoforms are involved in promoting cancer metastasis, sustaining cancer stem cell (CSC) properties, and conferring resistance to therapeutic interventions. Consequently, the development of monoclonal antibodies (mAbs) targeting CD44v represents a crucial strategy for eliminating CD44v-positive cancer cells. Previously, an anti-CD44v6 mAb, C₄₄Mab-9 (mouse IgG₁, κ), was established. C₄₄Mab-9 recognizes explicitly the epitope encoded by the variant exon 6-encoded region of CD44 and applies to flow cytometry, western blotting, and immunohistochemistry. To assess the therapeutic potential, a mouse IgG_2a isotype of C₄₄Mab-9 (designated C₄₄Mab-9-mG_2a) was generated, and the in vitro and in vivo antitumor activities were evaluated using gastric and colorectal cancer cell lines. C₄₄Mab-9-mG_2a demonstrated specific binding to CD44v3–10-overexpressed Chinese hamster ovary cells (CHO/CD44v3–10), as well as gastric cancer (NUGC-4) and colorectal cancer (COLO201 and COLO205) in flow cytometry. C₄₄Mab-9-mG_2a exerted antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against CHO/CD44v3–10, NUGC-4, COLO201, and COLO205. Moreover, systemic administration of C₄₄Mab-9-mG_2a significantly inhibited tumor growth in CHO/CD44v3–10, NUGC-4, COLO201, and COLO205 xenografts compared with the control IgG_2a. These findings indicate that C₄₄Mab-9-mG_2a could be applied to the mAb-based therapy against CD44v6-positive tumors. Full article