Allogeneic Cell Research Articles

TMOD-08. DETAILED GENERATION OF AN ORTHOTOPIC INTRACRANIAL GLIOBLASTOMA (GBM) PATIENT-DERIVED XENOGRAFT (PDX) MODEL FOR PRECLINICAL IMMUNOTHERAPEUTIC STUDIES

Abstract PURPOSE This study aimed to establish an orthotopic intracranial PDX mouse model using cryopreserved GBM tissues expanded in a heterotopic subcutaneous PDX model for immunotherapeutic studies. The model is designed to closely replicate human GBM, enabling the exploration of its pathophysiology and the development of effective immunotherapies for this type of cancer. METHODS Glioblastoma tissues from 16 fresh and cryopreserved samples were used to establish a heterotopic subcutaneous PDX mouse model for tumor expansion. Successful engraftments were then used to create an orthotopic intracranial PDX mouse model. The tumor formation rates and durations were estimated in both models. Tumor fidelity to the original GBM tumors was confirmed through immunohistology (GFAP, P53, and Ki67) and genetic analysis (whole exome sequencing, RNA sequencing, and methylome analysis). The therapeutic effects of immunotherapy (allogenic NK cells) in combination with Avastin and Irinotecan were tested in the orthotopic intracranial PDX model. RESULTS The orthotopic intracranial GBM mouse model achieved 100% engraftment from successful tumor growth in the subcutaneous PDX model. The overall success rate was 81.25% (85.71% for cryopreserved tissues), with a median process duration of 26.5 weeks (19 weeks for the subcutaneous and 7.5 weeks for intracranial establishment). No significant differences in tumor formation were observed within one year for cryopreserved tissue in the subcutaneous model. Molecular and genetic analysis confirmed similar tumor characteristics between the intracranial PDX tumors and the original patient tumors. Additionally, NK cells combined with Avastin and Irinotecan demonstrated efficacy in this model. CONCLUSIONS We successfully established an orthotopic intracranial PDX mouse model using cryopreserved GBM tissues, with no observed differences within one year. These models accurately mirror patients’ tumor characteristics, promising advancements in glioblastoma research and treatment, particularly for immunotherapy studies. Keywords: Glioblastoma (GBM), cryopreserved GBM tissues, patient-derived xenograft (PDX) model, NOD/SCID IL-12Rγnull (NSG) mice

A nanofibrous polycaprolactone/collagen neural guidance channel filled with sciatic allogeneic schwann cells and platelet-rich plasma for sciatic nerve repair.

Sciatic nerve damage, a common condition affecting approximately 2.8% of the US population, can lead to significant disability due to impaired nerve signal transmission, resulting in loss of sensation and motor function in the lower extremities. In this study, a neural guidance channel was developed by rolling a nanofibrous scaffold produced via electrospinning. The scaffold's microstructure, biocompatibility, biodegradation rate, porosity, mechanical properties, and hemocompatibility were evaluated. Platelet-rich plasma (PRP) activated with 30,000 allogeneic Schwann cells (SCs) was injected into the lumen of the channels following implantation into a rat model of sciatic nerve injury. Recovery of motor function, sensory function, and muscle re-innervation was assessed using the sciatic function index (SFI), hot plate latency time, and gastrocnemius muscle wet weight loss. Results showed mean hot plate latency times of Autograft: 7.03, PCL/collagen scaffolds loaded with PRP and SCs (PCLCOLPRPSCs): 8.34, polymer-only scaffolds (PCLCOL): 10.66, and untreated animals (Negative Control): 12.00. The mean SFI values at week eight were Autograft: -49.30, PCLCOLPRPSCs: -64.29, PCLCOL: -75.62, and Negative Control: -77.14. The PCLCOLPRPSCs group showed a more negative SFI compared to the Autograft group but performed better than both the PCLCOL and Negative Control groups. These findings suggest that the developed strategy enhanced sensory and functional recovery compared to the negative control and polymer-only scaffold groups.

Intra-Articular Injection of Human Umbilical Cord-Derived Mesenchymal Stromal Cells Reduces Radiographic Osteoarthritis in an Ovine Model.

To determine if mesenchymal stromal cells (MSCs) derived from human umbilical cords (hUC) could reduce degeneration developing when injected into the knee of a large animal model of osteoarthritis (OA). Ten million culture-expanded UC-MSCs (pooled from 3 human donors) were injected in 50 μL of tissue culture medium into the left stifle joints of 7 sheep whose medial meniscus was transected 4 weeks previously. Seven other sheep had only 50 μL of medium injected as the no treatment "control" group. After 8 weeks the sheep underwent euthanasia, the joints were excised and examined macroscopically, via x-ray and magnetic resonance imaging (MRI), both via histology for degenerative and inflammatory changes and immunohistochemically to identify any human cells within the joint tissues. Activity monitoring both before meniscus transection and euthanasia was also undertaken. There was a significant reduction in the Kellgren-Lawrence x-ray score for joints injected with hUC-MSCs compared with the control joints. Likewise, macroscopic, MRI, synovitis and OARSI histology scores were all lower (better) in the joints injected with hUC-MSCs than in the control arm, but not significantly. Activity levels and synovitis scores were similar in both groups of animals. hUC-MSCs appear to modify and reduce the development of osteoarthritic changes in the ovine stifle joint after meniscal destabilization, an injury which commonly leads to OA in humans. These results are encouraging for the potential benefit of culture expanded UC-MSCs as an allogeneic cell therapy in patients who may have early OA following a meniscal injury of the knee.

Construction a novel osteoporosis model in immune-deficient mice with natural ageing

Osteoporosis (OP) predominantly affects elderly individuals. Stem cells show potential for treating OP. However, animal models with normal immune function can eliminate implanted human cells. This study utilized naturally aging NOD/SCID mice, which exhibit immunodeficiency, to create a human osteoporosis model. This approach helps to minimize the premature immune clearance of transplanted allogeneic or xenogeneic cells in preclinical studies, allowing for a more accurate replication of the clinical pharmacological and pharmacokinetic processes involved in stem cell interventions for osteoporosis. NOD/SCID mice were fed until 12, 32, and 43 weeks of age, respectively, and then euthanized. We harvested lumbar vertebra for Micro‐Computed Tomography (Micro-CT) scanning and pathological examination. Additionally, we performed biomechanical testing of lumbar vertebra to assess the severity of osteoporosis. We utilized real-time RT-PCR to assess gene expression changes associated with bone metabolism, aging, inflammation, oxidative stress, and the Tgf-β1/Smad3 signaling pathway. In addition, the protein expression levels of P16, Tgf-β1 and Smad3 were detected using Western Blotting (WB). In comparison to 12-week-old mice, the 32-week-old and 43-week-old mice displayed significantly sparser and fractured trabeculae in their lumbar vertebra, lower bone mineral density (BMD), and changes in bone microstructural parameters (**P<0.01, ***P<0.001). Additionally, compared to 12-week-old mice, the 32-week-old and 43-week-old mice exhibited decreased expression of osteogenic genes (Alp, Opg, Sp7, Col1a1), increased expression of osteoclastic gene (Rankl), the number of TRAP-positive osteoclasts significantly increased in 32-week-old and 43-week-old mice compared to 12-week-old mice. The expression of genes related to aging and inflammatory (P16, Il-1β, Tnf-α) increases with advancing age (*P<0.05, **P<0.01, ***P<0.001). The expression of oxidative stress-related genes (Sod1, Sod2, Foxo3, Nrf2), as well as Tgf-β1 and Smad3 decreased with age (*P<0.05, **P<0.01, ***P<0.001). As age increases, the levels of P16 protein increase, Tgf-β1 and Smad3 proteins decrease. Our study successfully replicated osteoporosis models in NOD/SCID mice at both 32 and 43 weeks, with the latter exhibiting more severe osteoporosis. This condition seems to be driven by factors such as aging, inflammation, oxidative stress, and the Tgf-β1/Smad3 signaling pathway.

NK Cell-Based Cancer Immunotherapies: Current Progress, Challenges and Emerging Opportunities.

Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole-cell therapy, NK cell-derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell-based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research.

Harnessing Chimeric Antigen Receptor-engineered Invariant Natural Killer T Cells: Therapeutic Strategies for Cancer and the Tumor Microenvironment.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a revolutionary approach for cancer treatment, especially for hematologic cancers. However, CAR-T therapy has some limitations, including cytokine release syndrome (CRS), immune cellassociated neurologic syndrome (ICANS), and difficulty in targeting solid tumors and delivering allogeneic cell therapy due to graft-versus-host disease (GvHD). Therefore, it is important to explore other cell sources for CAR engineering. Invariant natural killer T (iNKT) cells are a potential target, as they possess powerful antitumor ability and do not recognize mismatched major histocompatibility complexes (MHCs) and protein antigens, thus avoiding the risk of GvHD. CAR-engineered iNKT (CAR-iNKT) cell therapy offers a promising new approach to cancer immunotherapy by overcoming the drawbacks of CAR-T cell therapy while retaining potent antitumor capabilities. This review summarizes the current CAR-iNKT cell products, their functions and phenotypes, and their potential for off-the-shelf cancer immunotherapy.

Developing endoscopic cell sheet delivery device using a beating human heart simulator and a pig model for minimally invasive cardiac regenerative therapy

Abstract Introduction Recently, clinical trials have commenced for cardiac regenerative therapy utilizing stem cells in patients with heart failure. Among the various transplantation approaches, there is a growing demand for less invasive methods to transplant sheet/patch-shaped cell products onto the heart surface, rather than resorting to conventional open surgery. This is particularly important considering the need for immunosuppressants due to allogeneic cell transplantation. Objective This study aims to develop a device for endoscopic transplantation of cell sheets onto the beating heart surface. Methods Prototype devices, initially developed in our prior study using a static heart model (Regenerative Therapy, 2020), were refined to better suit the cell sheet transplantation procedure onto a beating heart. We constructed a three-dimensional (3D) model of a beating heart located inside a thoracic cavity model, based on human computed tomography data and a 3D printer dedicated to simulating endoscopic surgical procedures. Human mesenchymal stromal cell (MSC)-derived cell sheets were prepared using temperature-responsive culture dishes and transferred onto a beating heart model pulsating at 80 beats per minute. We assessed the technical feasibility (N=8). Furthermore, skeletal muscle tissue was harvested from the thigh of the Clawn miniature pigs, and skeletal myoblasts were cultured from enzymatically digested tissue to create a cell sheet for autologous transplantation (8.0×10⁶ cells/sheet). Subsequently, the cell sheets labeled with Hoechst 33342 were endoscopically transplanted onto the pig heart surface (N=2). The pigs were sacrificed one week later, and the engraftment of the cell sheet was histologically evaluated. Results Successful deployment of MSC sheets onto the beating heart model was achieved in all procedures with one trial (100% success rate). The procedure duration from device insertion to the completion of cell sheet transplantation averaged 142±19 seconds. In experiments on autologous transplantation of myoblast cell sheets, two cases were successfully accomplished, with the transplanted cell sheet positive for Hoechst 33342 observed on the heart surface. Conclusion We have developed an endoscopic cell sheet delivery device using a pulsating heart model and a pig model, which holds promise for minimally invasive cardiac regenerative therapy in the future. Further investigations into the safety of the procedure are warranted for the clinical application of this system.

Cellular therapy for traumatic brain injury in adults: a meta-analysis of controlled clinical trials

IntroductionTraumatic brain injury (TBI) has got no effective treatment. Cellular therapy is the transfer of autologous or allogeneic cells or cellular material into patient(s) for treatment, showed better outcomes in TBI in several clinical and preclinical studies. We performed a meta-analysis on published articles on the topic of cellular therapy for the treatment of TBI in adult patients.Material and MethodsThe literature search was done via selected database with no restrictions on publication year. Studies were included based on selection criteria and quality assessment. The following data were extracted from included articles; author names, publication year and place, type of study, number, sex and age of participants, type of cells used, and post-treatment follow up. The required data related to Fugl-Meyer Motor Scale (FMMS), Disability Rating Scale (DRS) and patients. Overall improvement was pooled and analyzed using RevMan (Ver.5.4.1).ResultsFive studies that met the selection criteria and considered as high quality, containing 367 participants, with an average follow up time of (7.58±6.93) months, were included in meta-analysis. The results showed that cellular therapy significantly improves (OR=0.26; 95% CI=0.15 to 0.48; P=0.0001) the overall performance of the patients. Moreover, the improvements in FMMS (MD=3.79; 95% CI= -2.53 to 10.10; P=0.24) and DRS (MD= -0.16; 95% CI= -1.51 to 1.19; P=0.82) were not statically significant, but they are obviously clinically significant.ConclusionsThis meta-analysis suggests that cellular therapy improves the condition of TBI patients in clinic. Larger, multi-central trials are required to further confirm and detail the use of stem cells in TBI.

Application of biomedical cell products in the treatment of congenital epidermolysis bullosa

Congenital epidermolysis bullosa is a phenotypically and genetically heterogeneous group of genodermatoses, which which is clinically manifested by the development of blisters on the skin and mucous membranes after mechanical injury. The presence of long-term erosive and ulcerative defects in patients with congenital epidermolysis bullosa reduces the quality of patients` life and also leads to malignancy of the lesions, as a result of constant stimulation of regenerative processes.Currently, there are a lot of publications describing the use of skin substitutes, three-dimensional tissue-engineered structures based on auto- and allogeneic cells that promote rapid epithelization of wounds in patients with congenital epidermolysis bullosa. The most prospective and at the same time the least studied direction of congenital epidermolysis bullosa treatment is the use of a combined skin equivalent created on the basis of keratinocytes and fibroblasts, which mixes the advantages of epidermal and dermal grafts.

MG4101, an allogeneic natural killer cell, in patients with relapsed or refractory acute myeloid leukemia: a pilot study

We evaluated the safety and efficacy of allogeneic, ex-vivo expanded, NK cells, MG4101, in patients with refractory or relapsed AML. The relationship between immunological characteristics and clinical responses was analyzed. Between April 2018 and February 2020, 11 patients (male:female = 5:6) were treated with MG4101. Of eight evaluable patients, two (25.0%) showed partial response and two (25.0%) showed stable disease. The median overall survival was 3.4 months (95% confidence interval [95% CI], 2.5–4.3 months), and the allogeneic hematopoietic stem cell transplantation (HSCT) censored duration of response was 2.9 months (95% CI, 1.5–4.4 months). Two patients underwent HSCT after MG4101 treatment. Except for one grade 3 infusion-related reaction, no serious adverse events were observed. The sum of activating KIRs in responders tended to be higher than that in non-responders. Analyses of NKRL and KIR highlighted the importance of immunological mechanisms in treating myeloid neoplasms.

Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

ObjectivesTo assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP).MethodsParticipants were...

Transfusion Risk in Open, Laparoscopic, and Robotic-Assisted Surgery: A Propensity Score Matched Case-Control Study across Surgical Disciplines

Introduction: Robotic-assisted surgery is increasingly performed in various surgical disciplines demonstrating improved oncological and functional outcomes compared to conventional surgery. Objective: Unclear is how robotic-assisted surgery affects perioperative anemia and the need for blood products. Methods: In this case-control study, 15,009 matched patient pairs undergoing urological, visceral, or thoracic surgery were included. Pairwise comparisons between robotic-assisted surgery, laparoscopic surgery, and open surgery were performed with propensity score matching. Results: Robotic-assisted surgery compared to open surgery was associated with a risk reduction of allogeneic red blood cell transfusion by RR: 0.32 (95% CI: 0.27–0.37) and a limited reduction of perioperative hemoglobin (perioperative hemoglobin difference of 0.40 g/dL, 95% CI: 0.31–0.49). Robotic-assisted surgery was associated with a shorter length of hospital stay by 4.29 days (95% CI: 3.74–4.84). Compared to laparoscopic surgery, robotic-assisted surgery had no significant effect on red blood cell transfusions (RR: 0.94, 95% CI: 0.75–1.18), perioperative hemoglobin (0.27 g/dL, 95% CI: 0.16–0.38), or length of hospital stay 0.53 days (95% CI: −0.14–1.19). Conclusions: Robotic-assisted and laparoscopic procedures are associated with reduced blood transfusions compared to open surgery and, thus the advancement of minimally invasive procedures constitutes an important measure to improve patient outcomes.

Downregulating human leucocyte antigens on mesenchymal stromal cells by epigenetically repressing a β2-microglobulin super-enhancer.

Immune rejection caused by mismatches in human leucocyte antigens (HLAs) remains a major obstacle to the success of allogeneic cell therapies. Current strategies for the generation of 'universal' immune-compatible cells, particularly the editing of HLA class I (HLA-I) genes or the modulation of proteins that inhibit natural killer cells, often result in genomic instability or cellular cytotoxicity. Here we show that a β2-microglobulin super-enhancer (B2M-SE) that is responsive to interferon-γ is a critical regulator of the expression of HLA-I on mesenchymal stromal cells (MSCs). Targeted epigenetic repression of B2M-SE in MSCs reduced the surface expression of HLA-I below the threshold required to activate allogenic T cells while maintaining levels sufficient to evade cytotoxicity mediated by natural killer cells. In a humanized mouse model, the epigenetically edited MSCs demonstrated improved survival by evading the immune system, allowing them to exert enhanced therapeutic effects on LPS-induced acute lung injury. Targeted epigenetic repression of B2M-SE may facilitate the development of off-the-shelf cell sources for allogeneic cell therapy.

Abstract A049: NKG2D and NKp30 activating receptors drive allogeneic natural killer cell responsiveness against pancreatic cancer

Abstract A049: NKG2D and NKp30 activating receptors drive allogeneic natural killer cell responsiveness against pancreatic cancer

Cytokine-armed vaccinia virus promotes cytotoxicity toward pancreatic carcinoma cells via activation of human intermediary CD56dimCD16dim natural killer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-reserve vaccinia viruses (vvDD-IL2 and vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection weremeasured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine-armed virus targets the carcinoma cells and thus hasgreat potential to modulate the TIME in PDAC.

Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions.

Stem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.

High-dimensional analysis of NK cells in kidney transplantation uncovers subsets associated with antibody-independent graft dysfunction.

Natural Killer (NK) cells respond to diseased and allogeneic cells through NKG2A/HLA-E or Killer-cell Immunoglobulin-like receptor (KIR)/HLA-ABC interactions. Correlations between HLA/KIR disparities and kidney transplant pathology suggest an antibody-independent pathogenic role for NK cells in transplantation, but mechanisms remain unclear. Using CyTOF to characterize recipient peripheral NK cell phenotypes and function, we observed diverse NK cell subsets amongst participants that responded heterogeneously to allo-stimulators. NKG2A+/KIR+ NK cells responded more vigorously than other subsets, and this heightened response persisted post-kidney-transplant despite immunosuppression. In test and validation sets from two clinical trials, pre-transplant donor-induced release of cytotoxicity mediator, Ksp37, by NKG2A+ NK cells correlated with reduced long-term allograft function. Separate analyses showed Ksp37 gene expression in allograft biopsies lacking histological rejection correlated with death censored graft loss. Our findings support an antibody-independent role for NK cells in transplant injury and support further testing of pre-transplant, donor-reactive, NK cell-produced Ksp37 as a risk-assessing, transplantation biomarker.

Universal protection of allogeneic T-cell therapies from natural killer cells via CD300a agonism

AbstractImmunogenicity limits the persistence of off-the-shelf allogeneic cell therapies and transplants. Although ablation of HLA removes most T cell and humoral alloreactivity, no solution has enabled universal protection against the resulting natural killer (NK) cell response. Here, we engineered trans-antigen signaling receptors (TASRs) as a new class of NK inhibitory ligands and discovered CD300a, a previously inaccessible receptor, as a functional target. CD300a TASR outperformed leading alternative strategies in focused screens, including CD47 and HLA-E, and was solely capable of universally protecting allogeneic T cells against a large human cohort (45/45 donors), spanning diverse demographics and NK cell phenotypes. A model allogeneic T-cell therapy coexpressing an anti-CD19 chimeric antigen receptor and CD300a TASR, produced using multiplexed nonviral integration, exhibited enhanced B-cell killing potency under allogeneic immune pressure. CD300 TASR represents a universal solution to NK alloreactivity, broadening the population that could be effectively treated by next-generation allogeneic cell therapies.

Allogeneic CAR-T cells for cancer immunotherapy.

Autologous chimeric antigen receptor (CAR)-modified T (CAR-T) cell therapy has displayed high efficacy in the treatment of hematological malignancies. Up to now, 11 autologous CAR-T cell products have been approved for the management of malignancies globally. However, the application of autologous CAR-T cell therapy has many individual limitations, long time-consuming, highly cost, and the risk of manufacturing failure. Indeed, some patients would not benefit from autologous CAR-T cell products because of rapid disease progression. Allogeneic CAR-T cells especially universal CAR-T (U-CAR-T) cell therapy are superior to these challenges of autologous CAR-T cells. In this review, we describe basic study and clinical trials of U-CAR-T cell therapeutic methods for malignancies. In addition, we summarize the problems encountered and potential solutions.

Assessment of a nutritional status of patients qualified for autologous and allogeneic heamatopoietic cell transplantation

Assessment of a nutritional status of patients qualified for autologous and allogeneic heamatopoietic cell transplantation