Cytori Therapeutics (United States)

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by challenges in social interaction, communication, and repetitive behaviors. Psychotherapeutic interventions must tailor to meet the specific needs of individuals with ASD, given their diverse presentation of symptoms and functioning levels. This narrative review explores the range of psychotherapies available for individuals with ASD, examining their methodologies, effectiveness, and suitability. By using targeted search terms such as “autism,” “autistic disorder,” “autism spectrum disorders,” “psychotherapy,” “psychological intervention,” and “psychosocial intervention,” an extensive review of publications in English from 2000 to 2024 was conducted. This review covered several databases, including Embase, PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar. The review identified ten major psychological interventions for the treatment of individuals with ASD: behavioral therapies, developmental therapies, cognitive behavioral therapy, social skills training, speech-language therapy, occupational therapy, family therapy, mindfulness-based interventions, parent-mediated interventions, and dance movement psychotherapy. The main text elaborates on the effects of each intervention on various aspects of ASD. By providing this comprehensive overview, clinicians can select appropriate therapeutic strategies that cater to the individual profiles of those with ASD, ultimately enhancing therapeutic outcomes and quality of life for this population.

BackgroundCYT-303 is a multifunctional bispecific NK engager (NKE) targeting NK cell activating receptor NKp46 and tumor antigen Glypican-3 (GPC3) expressed in HCC (hepatocellular carcinoma). Cytovia’s proprietary FLEX-NKTM platform utilizes a novel FLEX-linker and human IgG1 back bone to allow for simultaneous binding to targeted cancer cells and NK cells. We evaluated additional CYT-303 Fc effector functions and the impact of CYT-303 when added to peripheral blood NK cells (PBNK) in Hep3B tumor spheroid cytolysis and Hep3B tumor serial killing assays. CYT-303 pharmacokinetics and safety in non-human primates were also evaluated.MethodsCYT-303 Fc effector function against Hep3B tumors was evaluated for antibody dependent cellular phagocytosis (ADCP) using human macrophages differentiated from purified monocytes isolated from peripheral blood and for complement dependent cytotoxicity (CDC) in the presence of rabbit complement. Hep3B tumor spheroids were established in special U-bottom adhesive plates and tumor spheroid killing assays were conducted with PBNKs and CYT-303 using the Incucyte TM Live Cell Analysis System. Serial killing assays were conducted by repeatedly adding the same PBNK cells to fresh tumor cells and CYT-303 following each round of tumor killing. CYT-303 single dose range finding pharmacokinetics and safety and 4-week repeat dose safety studies were conducted in cynomolgus monkeys by intravenous infusion dosing at 6, 20 and 60 mg/kg doses.ResultsCYT-303 showed dose dependent ADCP by human macrophages against Hep3B tumors that was maximal at 0.4 ug/ml. CYT-303 also showed maximal CDC against Hep3B tumors at 0.4 – 2 ug/ml concentrations. CYT-303 in the presence of freshly isolated PBNKs showed increased time dependent killing of Hep3B tumor spheroids that peaked at 2-3 days following initiation of killing. This killing was enhanced in the presence of CYT-303 in a dose dependent manner. Furthermore, PBNK serial killing of Hep3B tumors was also enhanced by CYT-303. In the CYT-303 single dose range finding pharmacokinetics study in cynomolgus monkeys the Cmax and AUC0-168h values increased with dose and increases were approximately dose-proportional. CYT-303, half-lives (T1/2) ranged from 39 to 47.6 hrs and exposures persisted up to 1-week. No evidence for any cytokine release was observed. In the 4-week repeat dose toxicity study no CYT-303 related toxicities were observed, enabling CYT-303 clinical development.ConclusionsCYT-303 demonstrated potent ADCP and CDC against Hep3B tumors as well as Hep3B tumor spheroid and serial killing activities in the presence of PBNKs. Preclinical pharmacokinetics and safety study results in cynomolgus monkeys support CYT-303 clinical development.

BackgroundCYT-100 is a first-generation iPSC derived NK cell product in development for use in combination with NK cell engager antibody (NKE) CYT-303 targeted against NKp46 activation receptor on NK cells and Glypican-3 (GPC3) expressed in the tumor for treatment of hepatocellular carcinoma (HCC). The combination of CYT-100 and CYT-303 is expected to activate endogenous NK cells and provide additional functional NK cells in the HCC microenvironment. Here we describe preclinical characterization of CYT-100 alone or in combination with CYT-303. In addition, we compared CYT-100 expansion capacity potential to PBNKs (peripheral blood natural killer cells).MethodsCYT-100 immunophenotyping was conducted by flow cytometry using a panel of NK cell directed antibodies. Intracellular signaling following stimulation of CYT-100 with rIL-2 or rIL-15 was assessed using a phospho STAT-5 antibody by flow cytometry and cell growth monitored by counting cells using the flow cytometer or a cell counting kit (CCK8). Hep3B tumor spheroids were formed in special U-bottom adhesive plates and tumor spheroid killing assays were conducted using the IncucyteTM Live Cell Analysis System. Serial killing assays were conducted by repeatedly adding the same CYT-100 cells to fresh tumor cells following each round of tumor killing. The chromosome telomere length was assessed by a q-PCR assay.ResultsCYT-100 immunophenotyping results showed > 95% expression of CD56/CD45, high expression of all activating receptors, except CD16, and some chemokine receptors including CXCR3, and minimal expression of most inhibiting receptors. Stimulation with rIL-2 or rIL-15 resulted in tyrosine phosphorylation of STAT-5 and increased cell growth over a period of 6 days, comparable to PBNKs, demonstrating the capacity of these cells to expand in the presence of cytokines. CYT-100 showed increased time-dependent killing of Hep3B tumor spheroids that peaked 2–3 days following of initiation of killing. This killing was enhanced in the presence of CYT-303 in a dose dependent manner. Furthermore, CYT-100 showed serial killing of Hep3B tumors and this was enhanced in combination with CYT-303. Chromosome telomere length analysis of CYT-100 showed greater telomere length compared to that of PBNKs, suggesting greater expansion capacity potential of these cells.ConclusionsThe allogeneic IPSC derived NK cell product CYT-100 demonstrates cytotoxicity against hepatocellular carcinoma Hep3B cells, sensitivity to cytokine activation and expansion potential. The cytotoxicity of this iNK product is further enhanced by combination with the NK cell engager antibody CYT-303. These data support further development of the combination of iNK cells and NKEs as therapeutics for HCC.

Objectives: The ADVANCE clinical trial sought to define the safety, feasibility and efficacy of an intracoronary infusion of adipose derived regenerative cells in patients admitted with an acute ST-elevation myocardial infarction (STEMI) within 24 hours of successful primary PCI. Methods: In this randomized, double-blind, placebo-controlled trial (n=23, 2:1 randomization), within 24 hours of successful primary PCI following STEMI, a small volume liposuction was performed for fat harvest and ADRC isolation by an automated Celution® System, and intracoronary infusion within 12 hours of the liposuction. Results: 23 patients were enrolled to date (all male, age 58 years, BMI 28 kg/m 2 ). The liposuction procedure data are shown in the table TEMI patients were routinely treated with dual anti platelets and heparin. The decline in hemoglobin following the liposuction procedure from baseline over the 10 hours following the procedure was 10.2% ±7.6 (mean ± SD) Although two patients had >20% of Hb decline at anytime (maximum 20.8%), one of these patients returned to within 10% of baseline by 10 hours without transfusion. The liposuction procedure was completed in all but one patient (terminated early due to hypotension - resolved with termination of procedure). IC infusion of the ADRC suspension was performed successfully in all patients. No impediment of coronary TIMI flow was observed during or following cell infusion of these mesenchymal-like cells. No ventricular arrhythmias were observed during cell infusion. No major adverse cardiac or cerebral events (MACCE) occurred within 30 days of the procedures. Conclusion: Limited liposuction to harvest fat for ADRC stem cell isolation and subsequent intracoronary infusion of these autologous ADRCs can be performed safely in patients with acute STEMI under dual antiplatelets therapy, demonstrating feasibility of the therapeutic application of point-of-care cell therapy using ADRCs.

Background. Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited causal treatments. The use of cell therapy has been suggested as a potential modality to improve the course and outcome of AKI.Methods. We investigated the possible renoprotection of freshly isolated, uncultured adipose tissue-derived stem and regenerative cells (ADRCs) before and after cryopreservation in a rat ischemia–reperfusion (I–R) model of AKI.Results. We demonstrated that ADRC therapy drastically reduced mortality (survival 100% vs. 57%, ADRC vs. controls, respectively) and significantly reduced serum creatinine (sCr on Day 3: 3.03 ± 1.58 vs. 7.37 ± 2.32 mg/dL, ADRC vs. controls, respectively). Histological analysis further validated a significantly reduced intratubular cast formation, ameliorated acute tubular epithelial cell necrosis and mitigated macrophage infiltration. Furthermore, a reduced RNA expression of CXCL2 and IL-6 was found in the ADRC group which could explain the reduced macrophage recruitment. Use of cryopreserved ADRCs resulted in an equally high survival (90% vs. 33% in the control group) and similarly improved renal function (sCr on Day 3: 4.64 ± 2.43 vs. 7.24 ± 1.40 mg/dL in controls).Conclusions. Collectively, these results suggest a potential clinical role for ADRC therapy in patients with AKI. Importantly, cryopreservation of ADRCs could offer an autologous treatment strategy for patients who are at high risk for AKI during planned interventions.