Long-term follow-up of CD19 chimeric antigen receptor T cell therapy in acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.

Autologous CD19 CAR-T cell therapy for pediatric and adult systemic lupus erythematosus: A phase 1/2 trial.

Non-canonical myeloid cell populations are increasingly recognized as critical regulators of inflammation in neuroimmunological disease. Here, we investigate the role of alternatively activated neutrophils (aaN) in limiting encephalitogenic T cell responses during experimental autoimmune encephalomyelitis (EAE), a widely used model of multiple sclerosis. Arginase-1–expressing aaN were identified and characterized within central nervous system (CNS) infiltrates during EAE using flow cytometry, single-cell RNA sequencing, and fluorescent in situ hybridization (RNAscope) combined with immunohistochemistry. The immunomodulatory properties of aaN were evaluated in vitro using CD4⁺ T cell suppression assays and in vivo by adoptive transfer of ex vivo–generated aaN during the preclinical phase following encephalitogenic T-cell injection. aaN were consistently detected within the CNS throughout EAE and spatially co-localized with encephalitogenic T cells. Transcriptomic profiling of aaN revealed enrichment of pathways associated with regulation of T cell activation and immune suppression. CNS-derived aaN potently inhibited CD4⁺ T cell proliferation in vitro. Therapeutic augmentation of this population, via adoptive transfer of ex vivo–generated aaN into mice following the injection of encephalitogenic T cells, delayed clinical EAE onset, markedly reduced the accumulation of pathogenic T cells within CNS lesions, and significantly enhanced neuronal survival. Mechanistically, ex vivo–generated aaN suppressed T cell responses through a contact-dependent, PD-L1–independent pathway, indicating a previously unrecognized mode of neutrophil-mediated immunoregulation. These findings identify aaN as a previously underappreciated immunoregulatory population within the inflamed CNS that restrains pathogenic T cell responses and limits neuroinflammation during EAE. Collectively, our data support the therapeutic potential of strategies that augment aaN activity, including autologous aaN-based cell therapy or interventions that promote CNS homing, polarization, and persistence of endogenous aaN, as novel approaches for disease modification in multiple sclerosis.

Advanced therapies infrequently achieve complete fistula closure in patients with Crohn's disease (CD). The primary objective of the STOMP2 clinical trial was to determine whether the implantable autologous cell therapy AVB-114 is effective in inducing remission of persistent Crohn's perianal fistulas versus standard of care. Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional CD therapy. All enrolled subjects underwent surgical fistula optimization and adipose tissue biopsy collection (in order to manufacture AVB-114) followed by 1:1 randomization to either standard of care (repeat fistula optimization including seton replacement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 36 weeks, defined as closure of the external opening, no drainage of fluid despite gentle finger compression, and no collections >2cm in at least two of the three dimensions on MRI. Subjects at 14 U.S. sites were equally randomized to SoC (N=24) or AVB-114 (N=24). Week 36 combined remission was 8.3% and 45.8% for subjects randomized to SoC and AVB-114, respectively (38% difference, 95% CI 11-60%; p=0.0078). At Week 36, MRI revealed no subjects with collections >2cm, radiological improvement (≥50% decrease in the MAGNIFI-CD score from baseline) in 1 SoC subject and 3 AVB-114 subjects, and radiological healing (complete resolution of T2-weighted hyperintensity in fistula tract) in 2 SoC subjects and 5 AVB-114 subjects. Through Week 36, there were 40 and 56 treatment emergent adverse events (TEAE) for SoC and AVB-114, respectively. There were no serious TEAEs in the AVB-114 group through Week 36. A significantly higher proportion of patients treated with AVB-114 achieved combined remission versus SoC, and the treatment was well tolerated. These data support the safety and efficacy of AVB-114 in persistent Crohn's perianal fistulas.

Lymphoma constitutes 24% of canine neoplastic diseases and 85% of haematopoietic tumours, with B-cell subtypes accounting for 60%-80% of cases. As the most prevalent spontaneous tumour in canines, this disease model holds significant translational value for human non-Hodgkin lymphoma research. To address diagnostic limitations in canine B-cell lymphoma, we developed a canine-specific CD19 monoclonal antibody (HAC19.1) with high affinity and established a dual-platform detection system compatible with flow cytometry and immunohistochemistry. Additionally, a novel CD19-targeting chimeric antigen receptor (CAR) gene sequence (HUA-1) was engineered and successfully transduced into Jurkat cells via lentiviral vectors, confirming stable CAR membrane expression. This breakthrough provides critical technical groundwork for advancing autologous CAR-T cell therapy in canines.

Chondromalacia patellae (CMP) is a degenerative disorder of the hyaline cartilage of the patella, forming part of the patellofemoral joint. Due to its key role in joint biomechanics, CMP commonly manifests as anterior knee pain and functional limitation, which can significantly impair patients’ quality of life. Early and accurate diagnosis, along with appropriate treatment, is crucial due to the very limited regenerative capacity of articular cartilage. This narrative review analyses current evidence regarding the etiology, diagnostic approaches, and treatment options for CMP, including conservative management, regenerative therapies (autologous chondrocyte implantation and mesenchymal stem cell therapy), and surgical interventions. A comprehensive literature search of the PubMed database (2010–2025) was performed, prioritising meta-analyses, systematic reviews, and randomised controlled trials relevant to the topic. CMP represents a complex degenerative condition requiring an integrated clinical and imaging-based approach. Magnetic resonance imaging is highlighted as the primary non-invasive diagnostic modality, while evidence supporting regenerative therapies remains promising but limited. Early recognition and tailored management strategies are essential to prevent disease progression and improve long-term functional outcomes.

Single-cell transcriptomics of multi-site cell therapy in osteoarthritis: Tissue-specific treatment correlations.

Relapse remains the primary cause of treatment failure and death in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Novel therapeutic approaches are imperative for those who are refractory to blinatumomab and chimeric antigen receptor T (CAR-T) cell therapy. CAR-natural killer (NK) cells have emerged as promising candidates for novel cancer immunotherapies, with enhanced antitumor activity and low rates of adverse events. However, data on the efficacy of CAR-NK cells for treating pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) are lacking.We report a challenging case of a boy with relapsed B-ALL after blinatumomab who failed to respond to autologous CD19-targeted CAR-T cell therapy and mitoxantrone-based reinduction chemotherapy. The patient achieved a complete remission after donor-derived CD19-targeted CAR-NK cell infusion, experiencing a grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), which was completely controlled by timely treatment. Then, the patient received the same donor-derived hematopoietic stem cell transplantation (HSCT) and remains in complete remission for a year post-HSCT.Our case provides an example of the utility of CAR-NK cell therapy as a bridge to HSCT in treating pediatric R/R B-ALL, despite the occurrence of ICANS as a manageable toxicity.

This retrospective analysis of the Cancer Analysis System registry in England describes the characteristics, systemic anti-cancer therapy (SACT) use, and survival outcomes of patients with multiple myeloma (MM), overall, by therapy line (L), and by autologous stem cell therapy (ASCT) status. Of 20,240 patients not on Cancer Drugs Fund therapies between January 2014 and December 2019, 12,095 had ≥ 1 SACT record and 3,419 received ASCT. Overall, regimens were aligned with national recommendations, but treatment sequencing differed by ASCT status, with 99.3% of ASCT patients subsequently receiving bortezomib-based regimens vs. 83.5% of non-ASCT patients. Time to next treatment or death decreased from 17.3 months at 1 L to 5.6 at 4 L, and was 47.4 months in patients receiving ASCT vs. 13.4 in non-ASCT patients at 1 L. Median overall survival also decreased by line of therapy, from 44.5 months at 1 L to 11.5 at 4 L. Approximately 77% of patients receiving ASCT survived > 60 months vs. 28% of non-ASCT patients. This study describes the real-world treatment landscape and survival outcomes for patients with MM on NHS funded treatments in England, highlighting differences between patients receiving ASCT and those not receiving it. It also demonstrates important data limitations and considerations for improvement.

To describe an unusual case of cytomegalovirus (CMV) retinitis presenting with significant vitreous inflammation in a lymphoma patient following combined autologous transplantation and chimeric antigen receptor (CAR) T cell therapy. This is a retrospective case report. The case was evaluated with multimodal ophthalmic imaging, and the diagnosis was established based on cytological and virological tests. A 54-year-old male with primary diffuse large B cell lymphoma of the cervical lymph nodes experienced monocular visual loss one month after combined autologous hematopoietic stem cell transplantation and CAR-T cell therapy. Initial examination revealed significant vitreous inflammation, mimicking intraocular lymphoma relapse. After the removal of dusty vitreous in the subsequent diagnostic vitrectomy, extensive retinal vascular occlusion emerged as the key feature with minimal retinal lesions. Cytological and virological studies of the vitreous sample excluded intraocular lymphoma and confirmed CMV retinitis. This case highlights prominent vitritis as an atypical presentation of CMV retinitis. This report broadens the recognized clinical spectrum of CMV retinitis, underscoring the necessity of considering CMV retinitis in the differential diagnosis of vitreous inflammation, particularly in lymphoma patients with complex immune statuses.

Stem cell therapy for spinal cord injury: lessons from Japan's experiment in regulatory deregulation.

Despite new treatments to delay disease progression in patients with diabetes and chronic kidney disease (CKD), many patients continue to lose kidney function and progress to kidney failure. Additional therapeutic strategies, perhaps targeting multiple deleterious pathways, are necessary to preserve kidney function in patients with advanced CKD. A multi-center, randomized, Phase 2 clinical trial (NCT05018416) assessed rilparencel (an autologous cell therapy composed of cells obtained by kidney biopsy), in participants with diabetes and estimated glomerular filtration rate (eGFR) 20 - 50 mL/min/1.73 m2. Participants were randomized 1:1 to two cohorts. Cohort 1 received two rilparencel injections percutaneously into the kidney cortex, three months apart, one in each kidney. Cohort 2 received one injection and a second injection only upon a sustained decline in eGFR or increase in urinary albumin creatinine ratio. Participants were followed up to 18 months after their last injection. The primary efficacy endpoint was change in eGFR slope from the pre- injection period to the period after the last injection. The primary safety endpoint was the percentage of participants with procedure or rilparencel-related treatment emergent adverse events (TEAEs). Fifty-three participants were randomized and 49 received at least one injection. In Cohort 1, annual eGFR slope (mL/min/1.73 m2/year) in the pre-injection period was -5.84 (standard error [SE] 1.07) versus -1.27 (SE 1.36) in the period after the last injection (difference 4.57 (95% confidence interval [CI] 1.95 to 7.18). In Cohort 2, annual eGFR slope in the pre-injection period was -3.40 (SE 0.81) versus -1.71 (SE 1.04) in the period after the last injection (difference 1.70 [95% CI -0.24 to 3.63]). No interactions were observed across multiple pre-defined baseline subgroups. Of 87 injections, procedure-related TEAEs occurred in 16 participants and rilparencel-related TEAEs occurred in six participants. No product-related serious adverse events and no procedure- or product-related deaths were reported. Bilateral kidney injection of rilparencel may preserve kidney function with an acceptable safety profile. A multi-center, Phase 3, randomized, sham-controlled study is ongoing.

Autologous CD133+ bone marrow-derived stem cell (BMDSC) therapy has been designated as an Orphan Drug by the EMA and FDA for the treatment of Asherman Syndrome (AS). This phase 1/2, non-randomized, open-label, single-arm trial assessed the safety and efficacy of this novel therapy in 20 infertile women with moderate to severe AS, unresponsive to prior hysteroscopic treatments. Primary endpoints were safety and tolerability over 15 months follow-up, including during pregnancy and after live birth. The therapy was well tolerated with a mean dosage of 125.41 × 106 cells, with no treatment-related serious adverse events and only reversible events such as arm pain, headache, and nausea. In pregnant patients, minor obstetric complications were reflux-related cough (n = 1), gestational diabetes (n = 2), cervical shortening requiring pessary placement (n = 2), and postpartum placenta accreta (n = 1). No preterm labor occurred, and all six newborns remained free of significant adverse events. Our findings suggest that autologous CD133 + BMDSC therapy is a safe and effective treatment for AS. Clinical trial registration (Eudra CT): 2016-003975-23.

Atrophic acne scars represent a therapeutic challenge with significant psychosocial impact. Autologous cell-based therapies, such as stromal vascular fraction (SVF) and the ReCell® system, aim to address the underlying dermal matrix deficiency through regenerative mechanisms. This systematic review and meta-analysis provides an updated and comprehensive quantitative synthesis of their standalone efficacy and safety. We conducted a systematic search of multiple databases (PubMed, Embase, Cochrane Library, CNKI, Wanfang) from inception to December 2025 for randomized controlled trials (RCTs) and split-face studies comparing autologous cell therapies (SVF, ReCell, fat grafting) with control treatments (e.g., saline, laser alone) for atrophic acne scars. The primary outcome was the change in the ECCA grading score. Secondary outcomes included patient satisfaction, objective scar metrics, healing time, and adverse events. Data were pooled using random-effects models. Eighteen studies involving 500 participants were included. Autologous cell therapies significantly reduced ECCA scores compared to controls (Standardized Mean Difference [SMD] = -1.25, 95% CI: -1.80 to -0.70, p < 0.001; I2 = 65%). Subgroup analysis indicated the largest effect size for SVF-based therapies (SMD = -1.40). Patient satisfaction was significantly higher in intervention groups (Risk Ratio [RR] = 1.45, 95% CI: 1.24-1.70). Objective outcomes also favored cell therapies, with greater scar depth reduction (Mean Difference [MD] = -0.25mm, 95% CI: 0.41 to -0.10) and accelerated wound healing (MD = -2.5days, 95% CI: 3.9 to -1.1). The overall incidence of adverse events was lower in the intervention groups (RR = 0.70, 95% CI: 0.50-0.98). Autologous cell-based therapies, particularly SVF, are effective and safe for improving atrophic acne scars, offering superior clinical, patient-reported, and safety outcomes compared to standard controls. The integration of detailed methodological insights provides a valuable evidence base to guide clinical protocol optimization and future research focused on standardization and long-term efficacy.

Abstract Background Perianal fistulizing Crohn’s Disease (PFCD) is associated with significant therapeutic challenges, poorer prognosis and reduced quality of life1. This aggressive phenotype is observed in 41.3% of Crohn’s Disease (CD) patients in our service2. Refractoriness and frequent reoperations highlight the need for more effective treatment alternatives3. Nanofat-based autologous stem cell therapy has shown promising results and high cost-effectiveness, an essential advantage in the healthcare systems of developing countries3,4. This study aimed to assess clinical healing at six months, characterized by the complete closure of all treated external openings (EO) and tracts, with no evidence of drainage, even upon external pressure. Methods Patients aged 18 years or older with PFCD refractory to standard medical therapy, without clinical, laboratory, or endoscopic rectal activity from a Brazilian tertiary public hospital were included. Prior to the definitive procedure, all patients underwent examination under anesthesia (EUA), fistula tract curettage, and seton placement. The surgical protocol consisted of seton removal, irrigation and curettage of the fistulous tracts, excision of the EO, closure of the internal openings (IO) using interrupted 3-0 absorbable sutures, followed by the application of nanofat (≈ 40 mL) at the IO region and into the tissue surrounding the fistulous tract. For the nanofat preparation approximately 100 mL of subcutaneous adipose tissue was harvested from abdominal or medial thigh region. The aspirate was decanted to obtain microfragmented fat (microfat), which was subsequently emulsified and filtered to obtain the nanofat4. The study was approved by the institutional ethics committee. Statistical analyses were performed using SPSS version 21.0 (SPSS, Chicago, IL, USA). Results Ten patients were submitted to the technique between April 2024 and May 2025, with a median age of 26,5 years and a median BMI of 23,7 kg/m². At six months, 90% of the patients met the criteria for clinical healing. The PDAI decreased from a median of 5.5 to 0 points. Over a median of 14,5 months (from 6 to 19 months) of follow-up, no recurrences and relevant adverse events related to liposuction or nanofat application were observed. Conclusion Autologous nanofat injection was a safe and effective surgical technique for the treatment of PFCD. Given its low cost and efficacy, this technique may represent an affordable treatment option, particularly in developing countries.

Autologous bone marrow cell therapy in autism: a case report

Knee osteoarthritis (OA) causes pain and disability, and autologous adipose-derived stem cell (ASC) therapy has emerged as a regenerative treatment option. This retrospective cohort study compared short-term outcomes of intra-articular ASC injections between patients with moderate (Kellgren–Lawrence [KL] 2/3) and severe (KL 4) OA. Among 242 treated patients, 98 in each group were analyzed after propensity score matching for age, sex, and body mass index. Pain (VAS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales were evaluated at baseline and 1, 3, and 6 months. Both groups showed significant improvements in pain and function, with KL 2/3 patients exhibiting greater gains in KOOS Total, Activities of Daily Living, Sports/Recreation, Quality of Life, and VAS pain compared with KL 4. KOOS pain and symptoms improved similarly in both groups. Analgesic effects increased over time, and no serious adverse events were observed. Mild transient swelling or discomfort occurred in about 5% to 6% of cases. ASC injections provided meaningful symptom relief and functional improvement, particularly in moderate OA, suggesting that preserved joint structure benefits therapeutic efficacy. In advanced OA, benefits were present but attenuated, indicating limited regenerative potential in end-stage disease.

Autologous CAR-T cell therapy has demonstrated remarkable clinical efficacy in hematologic malignancies, yet its broader application remains limited by complex, labor-intensive cell therapy manufacturing and inconsistent product quality. We describe a novel microfluidic cell separation platform based on deterministic lateral displacement (DLD), integrated into a fully automated, closed-system instrument (Curate system). N = 150 leukopacks were processed at a flow rate of 400 mL h-1 with processed volumes up to 250 mL, white blood cell concentrations up to 168 M mL-1 and total white blood cell counts up to 24 billion white blood cells. Compared to Ficoll®-based density gradient centrifugation, microfluidic DLD processing yielded significantly higher leukocyte recovery (88% vs. 58%), superior platelet and red blood cell depletion, and reduced CD69+ T cell activation. Flow cytometric analysis revealed improved phenotypic preservation across key T cell subsets, including naïve and central memory populations. Cytokine profiling demonstrated enhanced washing efficiency, with markedly lower levels of biologic response modifiers. DLD-purified T cells exhibited enhanced expansion kinetics and greater yield, supporting improved manufacturing outcomes. These findings position microfluidic DLD-based processing as a clinically relevant, scalable alternative to conventional methods, with potential to improve consistency, potency, and accessibility of CAR-T therapies.

Mesenchymal stem cells (MSCs) isolated from peripheral blood (PB) are gaining increasing attention among both researchers and clinicians, representing a promising alternative to traditional stem cell sources such as bone marrow and adipose tissue. Their therapeutic use offers key advantages like high accessibility, minimally invasive collection and autologous nature of the graft. Together with the ability to differentiate into multiple cell types, PB-MSC features make them ideal candidates for a wide range of clinical applications in the fields of regenerative medicine, tissue engineering and immunotherapy. While the therapeutic potential of PB-derived MSCs is more and more acknowledged, several challenges still need to be overcome regarding, for example, their isolation, expansion, and differentiation efficiency. For clinical translation, PB-MSC administration may be specifically indicated when minimally invasive autologous cell therapies are required, especially when bone marrow harvest is not recommended due to age, comorbidity, or prior surgeries. Conversely, PB-MSC auto-transplant should be avoided in patients suffering from hematological malignancies, active infections, or bone marrow disorders, where circulating stem cell populations may be altered, or their isolation poses safety risks. In this Perspective, we highlight recent advances in PB-MSC isolation and characterization, discuss their bioengineering integration into osteochondral repair strategies, and examine their immunomodulatory potential in osteoarthritis (OA). We propose that PB-MSCs integrate regenerative and immunomodulatory properties, positioning them as a promising, autologous cell source for next-generation personalized regenerative therapies. However, their clinical translation critically depends on the development of reproducible, GMP-compliant expansion protocols and validated potency assays.

Abstract Background The STOMP2 trial sought to determine whether the implantable autologous cell therapy AVB-114 is an effective add-on therapy for patients with persistent Crohn’s perianal fistulas. The trial design incorporated wait-list controlled (WLC) elements, allowing eligible control group subjects who completed the 9 mo primary endpoint visit in Part 1 to request AVB-114 treatment in Part 2 and strengthen the evaluation of AVB-114’s safety and effectiveness. Methods Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional Crohn’s disease therapy. Subjects at 14 U.S. sites were randomized 1:1 to either standard of care (SoC; fistula optimization including seton placement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 9 mo, defined as no collections &amp;gt;2cm on MRI, visual closure of the external opening, and no drainage of fluid despite gentle finger compression. A logistic regression time from exposure model through 9 mo utilized complete Part 1 data and all available Part 2 data to estimate combined AVB-114 effectiveness. Results Part 1 combined remission (using Non-Responder Imputation) was 8.3% (2/24) for SoC and 45.8% (11/24) for AVB-114 (38% difference, 95% CI 11 – 60%, post-hoc p-value of 0.0078). Twenty SoC subjects were treated with AVB-114 in Part 2. Four of the 9 Part 2 subjects with 9 mo combined remission data available were in combined fistula remission (44.4%). No subjects failed 9 mo radiological remission (first component of the primary endpoint), thus clinical remission (composite of the latter two components) was equivalent to combined remission. AVB-114 clinical remission in Part 1 and Part 2 to-date were similar, and when combined provided narrower estimates with the same coverage (Figure 1). Mean (SD) 9 mo perianal disease activity index (PDAI) scores for SoC, Part 1 AVB-114, and Part 2 AVB-114 were 5.0 (2.6), 4.1 (2.9), and 3.8 (3.5), respectively. Lower 9 mo scores and decreases from baseline were independently associated with an increased probability of clinical remission. Two serious treatment-emergent adverse events (TEAEs; pseudopolyposis and proctalgia) occurred, with the latter attributed to AVB-114. Non-serious product related TEAE were predominantly related to postoperative perianal pain. Two grade 2 (moderate) AEs of cellulitis and abdominal wall abscess were attributed to adipose tissue collection. Conclusion Both the randomized and combined (all-treated) analyses demonstrated substantial AVB-114 effectiveness through 9 mo in this challenging patient population. AEs were anticipated, and generally mild and infrequent. Conflict of interest: Schwartz, David: 1) Abbvie: consultant 2) Janssen: Consultant 3) Takeda: Consultant 4) Avbios- consultant 5) Olympus- consultant Dozois, Eric: TBD Ehman, Eric: TBD Faubion, William: TBD Hudesman, David: Consultant: Avalo, Abbvie, Abivax, Biocon, BMS, CorEvitas, Eli Lilly, Johnson and Johnson, Pfizer, Prometheus, Sanofi, Takeda, Fresenius Kabi Research Support: Pfizer and Johnson and Johnson Espen, Benjamin: employee of Avobis Bio LLC Pabla, Baldeep: Astellas, J &amp; J - Advisory Board Prometheus - Speaker Eli Lilly - Speaker Papadakis, Konstantinos: TBD