Simulect (basiliximab)

P=N/A, N=75, Not yet recruiting, Mario Negri Institute for Pharmacological Research

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P1, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

P1, N=12, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

P1, N=15, Active, not recruiting, University of Chicago | Trial completion date: Sep 2023 --> Sep 2025 | Trial primary completion date: Sep 2023 --> Sep 2025

P2, N=149, Completed, Astellas Pharma Global Development, Inc. | Phase classification: P2a --> P2

However, marketed anti-CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL-2 binding to CD25 on Teffs, which in turn destroys the function of Teffs. Moreover, our findings reveal that the Fab form of h7B7-15S has the ability to deplete Tregs, independent of the Fc region. Taken together, our studies expand the application of anti-CD25 in tumor immunotherapy and provide insight into the underlying mechanism.

P2, N=2, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed | N=20 --> 2

P4, N=80, Recruiting, University of Southern California | Trial completion date: Feb 2023 --> Feb 2025 | Trial primary completion date: Feb 2023 --> Feb 2025

We describe 3 cases of GVHD-associated cytopenias marked by HSPC depletion and presence of CD25 (IL-2R alpha subunit)-positive activated T cells in the marrow that responded to combinations of immunosuppression containing basiliximab (basil) anti-CD25 monoclonal antibody blockade...P1 received prednisone, CNI, and rituximab for a presumed anti-HSPC autoantibody...P3 has received prednisone, CNI, and sirolimus indefinitely for prevention of liver rejection and/or hepatocellular carcinoma relapse... We describe combined HSPC and T cell analyses in 3 patients (P) with severe GVHD-associated cytopenias. P1 was at 5 years post-HCT for acute lymphoblastic leukemia, P2 at 2 years post-HCT for severe aplastic anemia (SAA), and P3 at 1. 5 months post-liver transplant for alcohol use disorder-associated cirrhosis and hepatocellular carcinoma ( Table 1).

Here we show the experimental development of a third-generation CAR-NK therapy strategy against the CD25 based on the scFV of the clinically approved monoclonal humanized antibody, Basiliximab... We show here for the first time the potential use of an NK cell-mediated CAR therapy strategy targeting CD25 which has been shown to be upregulated in CML blast crisis. The experimental data show a significantly increased and selective in vitro and in vivo cytotoxicity of CD25 CAR-NK92 cells against CD25-expressing leukemia cells as compared to WT-NK92 cells. These results suggest that targeting CD25 by a CD25 CAR based on Basilixiamb's scFV might be an interesting tool in BC-CML and in all acute leukemias overexpressing CD25.

Background Although many reports have established the efficacy of post-transplantation cyclophosphamide (PTCy) or ATG for GVHD prophylaxis to in vitro non-T cell-depleted (non-TCD) haplo-HSCT and achieved a good clinical effect, the overall results of NRM, RI, DFS, and OS still need to be improved, especially for patients with high-risk or R/R hematologic malignancies...Our haplo-HDPSCT protocol was designed adopting high-dose in vitro non-TCD PBSCs as graft, Ara-C+Bu/Cy+rATG as the conditioning regimen, and Basiliximab plus short-term low-dose GCs added to standard GVHD prophylaxis...Only two patients in the haplo-HDPSCT group developed PTLD. Conclusions This study demonstrates that aGVHD is not high in our haplo-HDPSCT protocol and the long-term follow-up shows that this protocol may bring benefits including high engraftment rate, less relapse and viral infection, which implies that higher doses of in vitro non-TCD PBSCs as a graft source for haplo-HSCT protocol is feasible if appropriate GVHD prophylaxis is adopted.

P=N/A, N=958, Completed, Gang Chen

Adjunctive steroid therapy after pLT leads to earlier suppression of the post-pLT pro-inflammatory response and significantly reduced rejection rates during the first year after pLT (15.9%). 65% of patients initially treated without steroids remain steroid free over the first 12 months without rejection.

P2, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Nov 2024 --> Oct 2027

Basiliximab treatment administered on the basis of corticosteroid and CNI helped to effectively control the severe liver cGVHD, and basiliximab may provide a potential solution for these patients. Allogeneic hematopoietic stem cell transplant, Liver, Chronic graft-versus-host, Bilirubin

In addition to systemic steroids, basiliximab was the primary induction immunosuppression in 60% recipients with GVHD...Management strategies included combination of holding immunosuppression in 80% initially, use of systemic steroids in 50%, etanercept in 30%, ATG in 20%, and bone marrow transplant (BMT) in one... GVHD remains uncommon but fatal in LT recipients. In our experience, most cases present within the first 2-months after LT, and GVHD should be suspected when LT recipients develop skin rash, diarrhea, and/or pancytopenia. Skin only involvement portends a good prognosis, while multi-system involvement, and a wide Recipient-Donor age mismatch are poor prognosticators.

Recognizing that basiliximab was initiated for an “at-risk” patient population, this study demonstrates that monthly basiliximab infusions can be considered as an alternative maintenance immunosuppressive agent in pancreas transplant recipients who have failed other conventional agents.

P1, N=15, Active, not recruiting, University of Chicago | Trial completion date: Sep 2022 --> Sep 2023 | Trial primary completion date: Dec 2018 --> Sep 2023

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Dec 2023

P1, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2022 --> Dec 2023

He received basiliximab for induction IS and prednisone/tacrolimus/mycophenolate mofetil for maintenance IS...His fever, cytopenias and inflammatory markers improved with dexamethasone with no evidence of relapse. One year after his HLH diagnosis, he was evaluated for PTH-independent hypercalcemia (1,25OH-VitD 147pg/ml[20-79]): a whole-body PET/CT now showed diffuse hypermetabolic activity and a retroperitoneal mass biopsy revealed monomorphic DLBCL-PTLD.Results There have been reported cases of adult kidney transplant recipients developing HLH either concurrently with PTLD[1] or a few weeks following the PTLD diagnosis[2]. However, the diagnosis of HLH in our case preceded the identification of PTLD.Conclusion Therefore, our case illustrates that active surveillance for an underlying PTLD should be considered in transplant recipients when there is no initial evidence of malignancy at the time of HLH diagnosis, especially since hematologic malignancies are the most common trigger for HLH in adults.

P1, N=12, Recruiting, City of Hope Medical Center | Trial completion date: Jul 2024 --> Feb 2024 | Trial primary completion date: Jul 2024 --> Feb 2024

Immunosuppressive therapy with tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab was administered. The patient had urinary tract infections at 7 days, 9 weeks, and 4 months after kidney transplantation, and cytomegalovirus antigenemia at 9 weeks after kidney transplantation, which improved with antibiotic and valganciclovir, respectively...In this case, we believe that it was important to optimize the immunosuppressive therapy. In addition, from a review of previous cases, it seemed important that there was no GVHD requiring maintenance therapy in order to prevent excessive immunosuppression.

Induction with Basiliximab and maintenance: prednisone, MMF and tacrolimus. The majority of them are associated with solid organ transplantation and HIV infection. Current treatment include surgical resection, minimizing immunosuppression and sirolimus but further research is needed to establish the response to new treatments

Two recent studies from Japan showed that patients initially treated with a combination of high-dose corticosteroids, tacrolimus, and cyclophosphamide had higher 6-month survival than patients treated with high-dose corticosteroids followed by the addition of immunosuppressant agents. Other treatment options for patients with refractory illness include mycophenolate mofetil, rituximab, basiliximab, or tofacitinib... Anti-MDA5 antibody screening should be considered in all patients with RP-ILD even in the absence of cutaneous manifestations associated with CADM. More research is needed to help guide management and discover effective treatments options.

More importantly, PHA-activated hPBMC had much higher uptake of I-Basiliximab, indicating the potential utility of I-Basiliximab to discriminate activated hPBMC from its non-activated status. In summary, I-Basiliximab was fabricated for the first time, which can be applied in CD25-targeted immuno-PET imaging of activated T cells in vivo.

P2, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Apr 2023 --> Nov 2026 | Trial primary completion date: Apr 2023 --> Nov 2024

First line therapy remains discontinuation of the ICI and initiation of steroids, with some literature supporting T-cell-specific immunomodulators such as mycophenolate, tacrolimus, or azathioprine as second line agents...Design/ Case ReportA 22-year-old female with recurrent metastatic osteosarcoma of her right proximal tibia began treatment with the anti-PD-1 monoclonal antibody nivolumab for refractory disease...Given continued elevation in her LFTs, further treatments included everolimus, rabbit ATG, and tacrolimus, none of which were successful in persistently decreasing her LFTs, which peaked at greater than 20 times normal, indicating a Grade 4 adverse event... Basiliximab may be an effective therapy for steroid-resistant severe ICI associated hepatitis.

P2, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Nov 2023 --> Apr 2023 | Trial primary completion date: Nov 2023 --> Apr 2023

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2018 --> Jul 2021

P1, N=20, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022

P1, N=12, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Jun 2023 --> Jul 2024 | Initiation date: Dec 2021 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jul 2024

P1, N=12, Not yet recruiting, City of Hope Medical Center

Importantly, Basiliximab, a CD25-specific IL-2 blocking antibody, although efficient at depleting Treg cells, did not impact tumor growth, thus demonstrating that the IL-2 sparing feature of ALD2510 is critical to elicit anti-tumour response in vivo. Conclusions This preclinical data package supports CD25 as a potent and selective Treg marker allowing Tregs depletion while sparing conventional T cells. In this context, ALD2510, a novel humanized CD25-specific and IL-2 sparing antibody presents all the required attributes for selective and efficient TIL-Tregs depletion, making it a promising drug candidate to treat a broad range of solid tumor patients.

After a kidney transplant in 2015, immunosuppressive induction therapy was performed by basiliximab, and for the first 2 years, tacrolimus, mycophenolate mofetil, and prednisolone were taken...Prednisolone continued to be used, mycophenolate mofetil and tacrolimus were replaced by sirolimus. But after 1 month of using sirolimus this drug was replaced by cyclosporine A because of financial problem...Since February until June 2018, we did 6 courses of R-CHOP chemotherapy...A detailed examination should be needed to rule out any changes occurred in the transplant cases. The regular EBV infection monitoring is very important to patients with high immunosuppressive therapy.

P2, N=33, Recruiting, City of Hope Medical Center | Trial completion date: Apr 2023 --> Nov 2023 | Trial primary completion date: Apr 2023 --> Nov 2023

While these data support the rational to target CD25, ALL cells did not appear to be in-vitro sensitive to basiliximab, an antibody able to target the Il2RA, but in-vivo investigations are needed to better assess the effects of this therapeutic approach in ALL context...Targeting CD25 receptor with anti-CD25 antibodies or peptide mimetics could be an effective strategy for targeting leukemic cells. Additionally, high CD25 expression could be exploited for the development of CAR-T therapy

While these data support the rational to target CD25, ALL cells did not appear to be in-vitro sensitive to basiliximab, an antibody able to target the Il2RA, but in-vivo investigations are needed to better assess the effects of this therapeutic approach in ALL context...Targeting CD25 receptor with anti-CD25 antibodies or peptide mimetics could be an effective strategy for targeting leukemic cells. Additionally, high CD25 expression could be exploited for the development of CAR-T therapy