Increased donor inhibitory KIR are associated with reduced GVHD and improved survival following HLA-matched unrelated donor HCT in paediatric acute leukaemia.

Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated effects after haematopoietic stem cell transplantation (HCT). Previous work has shown that accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity in the adult transplant setting. Paediatric acute leukaemia patients were retrospectively analysed, and KIR-KIRL combinations and maximal inhibitory KIR ligand (IM-KIR) scores were determined. Clinical outcomes were examined using a series of graphs depicting clinical events and endpoints. The graph methodology demonstrated that prognostic variables significant in the occurrence of specific clinical endpoints remained significant for relevant downstream events. KIR-KIRL combinations were significantly predictive for reduced grade 3-4 aGVHD likelihood, in patients transplanted with increased inhibitory KIR gene content and IM-KIR = 5 scores. Improvements were also observed in associated outcomes for both ALL and AML patients, including relapse-free survival, GRFS and overall survival. This study demonstrates that NK cell KIR HLA interactions may be relevant to the paediatric acute leukaemia transplant setting. Reduction in aGVHD suggests KIR effects may extend beyond NK cells. Moving forward clinical trials utilizing donors with a higher iKIR should be considered for URD HCT in paediatric recipients with acute leukaemia to optimize clinical outcomes.

Advances in the ocular complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.

[Current state of graft-versus-host disease prophylaxis with PTCy for allogeneic hematopoietic stem cell transplantation].

There is growing recognition of post-transplant cyclophosphamide (PTCy) as the new standard prophylaxis for graft-versus-host disease (GVHD) in HLA-matched peripheral blood stem cell transplants with reduced intensity conditioning, based on recent results of randomized phase III trials of PTCy. Allogeneic hematopoietic cell transplantation (HCT) with PTCy is thought to have GVHD-dependent and -independent graft-versus-tumor (GVT) effects. Its GVHD-dependent effects may be attenuated by PTCy-induced alloreactive T cell dysfunction and preferential recovery of regulatory T cells after HCT, but its GVT effects do not appear to be significantly impaired in patients in remission or with indolent disease. As patients not in remission are often also candidates for transplantation in Japan, it will be necessary to use PTCy as a platform to establish a strategy that could also be effective in patients not in remission and to revise the donor selection algorithm.

Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study.

Introduction: Donor choosing remains to play a pivotal role in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous criteria beyond HLA compatibility impact the selection of a suitable donor. Methods: We evaluated the effect of donor parity on transplant outcomes in a large homogeneously treated population that received an HLA-matched allo-HSCT between 2010 and 2021 at our center. All patients were transplanted from a peripheral blood stem cell source following a myeloablative Busulfan-based conditioning and an identical protocol for graftversus-host disease (GVHD) prophylaxis regimen. Results: A total of 1103 allo-HSCT recipients were included. 188 (17%) had transplants from parous female donors, whereas 621 (56.30%) and 294 (26.70%) received transplants from male and nulliparous female donors, respectively. HSCTs from parous female donors compared to male and nulliparous females were associated with a significantly higher incidence of grade III-IV acute (a) GVHD (55.27% vs. 11.34 and 10.84%) and extensive chronic (c) GVHD (64.32% vs. 15.52 and 13.65%), as well as lower relapse incidence (RI). Discussion: This study finds that while parous female donors are associated with higher incidences of grade III-IV aGVHD and extensive cGVHD post-allo-HSCT, the advantages, such as a lower RI, outweigh the risks. The results of our study provide valuable insights for donor selection.

Corrigendum: Determining the predictive impact of donor parity on the outcomes of human leukocyte antigen matched hematopoietic stem cell transplants: a retrospective, single-center study.

[This corrects the article DOI: 10.3389/fonc.2024.1339605.].

Better clinical outcomes and lower triggering of inflammatory cytokines for allogeneic hematopoietic cell transplant recipients treated in home care versus hospital isolation - the Karolinska experience.

After allogeneic hematopoietic cell transplantation (Allo-HCT) and conditioning, patients are typically placed in isolated hospital rooms to prevent neutropenic infections. Since 1998, we've offered an alternative: home care for patients living within a one to two-hour drive of the hospital. In Sweden this approach includes daily visits by an experienced nurse and daily phone consultations with a unit physician. When necessary, patients receive transfusions, intravenous antibiotics, and total parenteral nutrition at home. Our initial study report compared 36 home care patients with 54 hospital-treated controls. Multivariate analysis found that home care patients were discharged earlier to outpatient clinics, required fewer days of total parenteral nutrition, had less acute graft-versus-host disease (GVHD) grade II-IV, and lower transplantation-related mortality (TRM) and lower costs. Long-term follow-up showed similar chronic GVHD and relapse rates in both groups, with improved survival rates in the home care group. A subsequent comparison of 146 home care patients with hospital-treated controls indicated that home care and longer home stays were associated with lower grades of acute GVHD. Home care was found to be safe and beneficial for children and adolescents. Over two decades, 252 patients received home care post-Allo-HCT without any fatalities at-home. Ten-year outcomes showed a 14% TRM and a 59% survival rate. In 2020, an independent center confirmed the reduced risk of acute GVHD grades II-IV for patients treated in home care. Here, we report for the first time that home care patients also demonstrate a less inflammatory systemic cytokine profile. We found higher levels of IFN-γ, IL-2, IL-5, IL-13, GM-CSF, and G-CSF, but lower VEGF in hospital-treated patients, which may contribute to acute GVHD grades II-IV. In conclusion, home-based treatment following Allo-HCT yields multiple promising clinical outcomes and improved systemic inflammatory markers, which may contribute to less development of life-threatening GVHD.

Human placental mesenchymal stromal cells promote the formation of CD8+CD122+PD-1+Tregs via CD73/Foxo1 to alleviate liver injury in graft-versus-host disease mice.

BACKGROUND: Human placental mesenchymal stromal cells (hPMSCs) are known to limit graft-versus-host disease (GVHD). CD8+CD122+PD-1+Tregs have been shown to improve the survival of GVHD mice. However, the regulatory roles of hPMSCs in this subgroup remain unclear. Here, the regulatory mechanism of hPMSCs in reducing liver fibrosis in GVHD mice by promoting CD8+CD122+PD-1+Tregs formation and controlling the balance of IL-6 and IL-10 were explored. METHODS: A GVHD mouse model was constructed using C57BL/6J and BALB/c mice and treated with hPMSCs. LX-2 cells were explored to study the effects of IL-6 and IL-10 on the activation of hepatic stellate cells (HSCs). The percentage of CD8+CD122+PD-1+Tregs and IL-10 secretion were determined using FCM. Changes in hepatic tissue were analysed by HE, Masson, multiple immunohistochemical staining and ELISA, and the effects of IL-6 and IL-10 on LX-2 cells were detected using western blotting. RESULTS: hPMSCs enhanced CD8+CD122+PD-1+Treg formation via the CD73/Foxo1 and promoted IL-10, p53, and MMP-8 levels, but inhibited IL-6, HLF, α-SMA, Col1α1, and Fn levels in the liver of GVHD mice through CD73. Positive and negative correlations of IL-6 and IL-10 between HLF were found in liver tissue, respectively. IL-6 upregulated HLF, α-SMA, and Col1α1 expression via JAK2/STAT3 pathway, whereas IL-10 upregulated p53 and inhibited α-SMA and Col1α1 expression in LX-2 cells by activating STAT3. CONCLUSIONS: hPMSCs promoted CD8+CD122+PD-1+Treg formation and IL-10 secretion but inhibited HSCs activation and α-SMA and Col1α1 expression by CD73, thus controlling the balance of IL-6 and IL-10, and alleviating liver injury in GVHD mice.

HLA-haploidentical T-cell receptor αßT/B-cell-depleted stem cell transplantation for Fanconi anemia.

HLA-haploidentical stem cell transplantation (haplo-SCT) using post-transplant high-dose cyclophosphamide (PT-CY) is an alternative choice when a suitable donors is unavailable. However, PT-CY is difficult in patients with Fanconi anemia (FA) due to their high vulnerability to alkylating agents. For FA, we prefer haplo-SCT by T-cell receptor αßT-cell and B-cell depletion (αßT/B-depleted haplo-SCT), which can reduce the risks of PT-CY-related complications and graft-versus-host disease (GVHD). An 11-year-old boy with diagnosed FA (FANCG mutation) and bone marrow failure was to receive αßT/B-depleted haplo-SCT from his father (HLA 4/8 allele matched) due to absence of an HLA-matched donors. αßT/B-depleted peripheral blood stem cells (CD34 + cell count, 1.17 × 107/kg; αß + T-cell count, 1.3 × 105/kg) were infused following conditioning consisting of fludarabine (150 mg/m2), cyclophosphamide (40 mg/kg), anti-thymocyte globulin (5 mg/kg), rituximab (375 mg/m2), and thoraco-abdominal irradiation (3 Gy). Tacrolimus was used for GVHD prophylaxis until day + 30. Neutrophil engraftment was achieved on day + 9, and complete chimerism was confirmed on days + 28 and + 96. At 12-month post-SCT, the patient was well without GVHD or any other complications. αßT/B-depleted haplo-SCT is a good choice not only for patients unsuitable for PT-CY, but also for all pediatric recipients to reduce SCT-related complications.

Lower incidence of grade II-IV acute Graft-versus-Host-Disease in pediatric patients recovering with high Vδ2+ T cells after allogeneic stem cell transplantation with unmanipulated bone marrow grafts: a prospective single-center cohort study.

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαß, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.

Role of Endoscopic Techniques in the Diagnosis of Complications of Allogeneic Hematopoietic Stem Cell Transplantation: A Review of the Literature.

Allogeneic stem cell transplantation (Allo-SCT) implies that a donor and a recipient are not genetically identical. Allo-SCT is used to cure a variety of conditions, including hematologic malignancies using the graft versus tumor effect, nonmalignant hematologic, immune deficiencies, and, more recently, genetic disorders and inborn errors of metabolism. Given the immunosuppressive and myeloablative nature of some of the conditioning chemotherapy regimens used during the Allo-SCT, patients are often at high risk of infection, including viral infections affecting the gastrointestinal tract, following the transplant. Furthermore, other complications such as hepatic sinusoidal obstruction syndrome (SOS) or graft-versus-host disease may occur post-transplant and may require endoscopy to assist in the diagnosis. This review will provide newer insights into the importance of endoscopic techniques in the diagnosis of post-Allo-SCT complications with a focus on safety and timing.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk-factors and outcomes are not well-understood due to a sparsity of cases spread across multiple centers. OBJECTIVES: The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplant-related risk factors and co-morbid critical care diagnoses associated with post-HCT DAH. STUDY DESIGN: Retrospective analysis was performed on a multi-center cohort of 6,995 patients ≤21 years old who underwent allogeneic HCT between 2008-2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox-proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox-regression with DAH as a time-varying covariate. RESULTS: DAH occurred in 81 patients at a median 54 days post-HCT (IQR 23-160 days), with a 1-year post-transplant cumulative incidence probability of 1.0% (95% CI 0.81-1.3%) and was noted in 7.6% of all PICU patients. Risk factors included transplant for non-malignant hematologic disease (Referent: malignant hematologic disease, HR=1.98, 95% CI 1.22-3.22, p=0.006), use of calcineurin inhibitor plus mycophenolate mofetil (CNI + MMF) as GvHD prophylaxis, (Referent: calcineurin inhibitor plus methotrexate, HR=1.89, 95% CI 1.07-3.34, p=0.029), and grade III-IV acute GvHD (HR=2.67, 95% CI 1.53-4.66, p<0.001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (p<0.05) than those without DAH. From the time of DAH, median survival was 2.2 months and one-year overall survival was 26% (95% CI 17-36%). Among all HCT patients, the development of DAH when considered was associated with a seven-fold increase in unadjusted all-cause post-HCT mortality (HR 6.96, 95% CI 5.42-8.94, p<0.001). In a landmark analysis of patients alive 2 months post-HCT, patients who developed DAH had a one-year overall survival of 33% (95% CI 18-49%) versus 82% (95% CI 81-83%) for patients without DAH (p<0.001). CONCLUSION: Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of non-malignant hematologic transplant indication, use of CNI + MMF as GvHD prophylaxis and severe acute GvHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

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.

Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.

The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.

Successful management of acute graft-versus-host disease with ibrutinib during cord blood transplantation for germline DDX41-mutated acute myeloid leukemia.

Background: Acute graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with significant morbidity and mortality, and efficacy of currently available therapeutics are limited. Acute and chronic GVHD are similar in that both are initiated by antigen presenting cells and activation of alloreactive B-cells and T-cells, subsequently leading to inflammation, tissue damage, and organ failure. One difference is that acute GVHD is mostly attributed to T-cell activation and cytokine release, whereas B-cells are the key players in chronic GVHD. Ibrutinib is an irreversible inhibitor of the Bruton's tyrosine kinase (BTK), which is part of B-cell receptor signaling. Ibrutinib is currently used for treating chronic GVHD, but its efficacy towards acute GVHD is unknown. Besides BTK, ibrutinib also inhibits interleukin-2 inducible T-cell kinase (ITK), which is predominantly expressed in T-cells and a crucial enzyme for activating the downstream pathway of TCR signaling. ITK activates PLCγ2 and facilitates signaling through NF-κB, NFAT, and MAPK, leading to activation and proliferation of T-cells and enhanced cytokine production. Therefore, the TCR signaling pathway is indispensable for development of acute GVHD, and ITK inhibition by ibrutinib would be a rational therapeutic approach. Case presentation: A 56-year-old male acute myeloid leukemia patient with Myeloid neoplasms with germline DEAD-box RNA helicase 41 (DDX41) mutation underwent cord blood transplantation and developed severe gastrointestinal (GI) acute GVHD which was refractory to steroids and mesenchymal stem cell therapy. While acute GVHD accommodated by multiple life-threatening GI bleeding events persisted, chronic cutaneous GVHD developed, and ibrutinib 420 mg/day was initiated from day 147 of transplant. Although ibrutinib was commenced targeting the chronic GVHD, unexpected and abrupt remission of acute GVHD along with remission of chronic GVHD was observed. Conclusion: Ibrutinib is a promising therapeutic for treating acute GVHD, and further studies are warranted.

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)