We provide experimental evidence that the synergic use of an anti-IL-10 antibody in combination with mifamurtide causes a significantly increased mortality rate in highest-grade OS cells and lower metastasis in an in vivo model compared with mifamurtide alone. Overall, our data suggest that mifamurtide in combination with an anti-IL-10 antibody could be proposed as a new treatment protocol to be studied to improve the outcomes of OS patients.
Initial treatment in this series of 295 patients with FL included monoclonal antibody + chemotherapy (57%), single-agent rituximab (15%), chemotherapy (2%), radiotherapy alone (8%), and other treatments (6%). Exploratory analysis with WES was performed on 16 FLEP cases and 10 FLLP cases. There were no significant differences in the occurrence of gene mutations between FLEP and FLLP cases in the WES cohort. Only 1 gene, SETD1B, appeared in the WES panel that is not covered in the HemePACT and clinical IMPACT targeted signaling platforms.
This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
2 years ago
P2 data • Retrospective data • Clinical Trial,Phase II • Journal
Here, we provide experimental evidence that the addition of an anti-IL-10 antibody to Mifamurtide causes a significant death rate in more aggressive osteosarcoma cells and lower metastasis, compared to Mifamurtide only. In conclusion, considering our data, it could be proposed a new treatment protocol for metastatic osteosarcoma that includes the use of an anti-IL10 antibody integrated with the administration of Mifamurtide to increase its effectiveness in this clinical context.
We identified potential immunotherapeutic agents based on prognostic gene signature: hexamethonium bromide and isoflupredone. Several novel candidate drugs were suggested, including human interferon-α-2b, paclitaxel, imiquimod, MESO-DAP1, and mifamurtide. These biomolecules and repurposed drugs may be utilised for prognosis and treatment for better survival.
Preoperatively, all patients received methotrexate, adriamycin, cisplatinum (MAP)...In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months then weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor histologic response (necrosis < 90%) to MAP... In this prospective uncontrolled study with a risk-adapted strategy for non-metastatic osteosarcoma, survival is superior to that of all ISG/GEIS previous series . The 3-year EFS of 71.9% compares favorably with other reports . Pgp+ patients performed well in this study, in which mifamurtide and HDIFO were added after a poor response to MAP.
P2/3, N=225, Active, not recruiting, Italian Sarcoma Group | Trial completion date: Mar 2021 --> Oct 2021 | Trial primary completion date: Mar 2021 --> Oct 2021
3 years ago
Clinical • Trial completion date • Trial primary completion date
TAMs may participate in the malignant progression of osteosarcoma through self-polarization, the promotion of blood vessel and lymphatic vessel formation, immunosuppression, and drug resistance. Besides, various immune checkpoint proteins expressed on the surface of TAMs, such as PD-1 and CD47, provide the possibility of the application of immune checkpoint inhibitors. Several clinical trials have been carried out and/or are in progress. Mifamotide and the immune checkpoint inhibitor Camrelizumab were both found to be effective in prolonging progression-free survival. Thus, TAMs may serve as attractive therapeutic targets. Targeting TAMs as a complementary therapy is expected to improve the prognosis of osteosarcoma. Further efforts may be made to identify potential beneficiaries of TAM-targeted therapies.
3 years ago
Review • Journal
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PD-1 (Programmed cell death 1) • CD47 (CD47 Molecule)
Preoperatively, all patients received MAP (methotrexate, adriamycin, platinum). In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months than weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor response (PR) to MAP...Funding: The Onlus Association “Il Pensatore - Matteo Amitrano”; Fondazione Carisbo Clinical and Translational Research Grant 2019. Clinical trial identification: NCT01459484; Eudract: 2011-001659-36.