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DRUG CLASS:

Macrophage stimulant

11d
Tumor microenvironment gene engineering with LOAd703 in patients with solid malignancies: LOKON002 phase I/IIb clinical trial. (PubMed, Clin Cancer Res)
TME gene engineering using LOAd703 inflamed immune cold tumors and was followed by long term stabilized disease in several patients. Further evaluation of LOAd703 together with chemotherapy and/or checkpoint inhibitors is warranted.
P1/2 data • Journal • IO biomarker
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CD40 (CD40 Molecule)
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gemcitabine • delolimogene mupadenorepvec (LOAd703)
1m
Reprogramming myeloid cells and restoring T cell fitness in checkpoint inhibitor resistant melanoma patients. (PubMed, Biomark Res)
Collectively, the results propose that treatment with LOAd703 and atezolizumab induce an immune phenotype of ICI resistant patients that has previously been reported associative with ICI responsiveness. These results merits further clinical investigation of supplementary LOAd703 treatment to accomplish ICI sensitivity in ICI resistant MM.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • CD40LG (CD40 ligand)
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Tecentriq (atezolizumab) • delolimogene mupadenorepvec (LOAd703)
2ms
Safety of intratumoral immunostimulatory LOAd703 gene therapy combined with chemotherapy in patients with advanced cancer. (PubMed, Immunooncol Technol)
LOAd703 was administered every 2 weeks by ultrasound-guided intratumoral injections, combined with a standard-of-care or immune-conditioning gemcitabine-based chemotherapy regimen. A trend of higher interferon-gamma (IFN-γ) plasma levels in the highest LOAd703 dose cohort was observed. The acceptable toxicity associated with LOAd703 and chemotherapy, combined with signs of clinical benefit in poor prognostic cancer patients, warrant further studies.
Journal
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IFNG (Interferon, gamma) • CD40LG (CD40 ligand)
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gemcitabine • delolimogene mupadenorepvec (LOAd703)
2ms
The Dual Mechanism of Action of CO-005 Overcomes CD20 Resistance in Diffuse Large B-Cell Lymphoma. (PubMed, Immunotargets Ther)
Despite the clinical success of anti-CD20 monoclonal antibodies (mAbs) such as rituximab in the treatment of B-cell lymphoma, therapeutic resistance and relapse remain significant challenges, particularly in tumors with low or heterogeneous CD20 expression resulting from antigen loss or phenotypic shifts. In vivo, CO-005 triggered robust intratumoral PCCD and remodelled the tumor microenvironment, characterized by increased macrophage and neutrophil infiltration, thereby enhancing innate immune activation and supporting a dual-mechanism mode of action that couples direct cancer cell killing with myeloid engagement. These findings position CO-005 as a mechanistically distinct and immunologically active therapeutic with the potential to overcome limitations of both CD20- and CD47-directed therapies and expand treatment options for B-cell lymphoma.
Journal
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CD20 (Membrane Spanning 4-Domains A1) • CALR (Calreticulin) • SIRPA (Signal Regulatory Protein Alpha)
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Rituxan (rituximab)
2ms
LOKON001: LOAd703 Oncolytic Virus Therapy for Pancreatic Cancer (clinicaltrials.gov)
P1/2, N=51, Completed, Lokon Pharma AB | Active, not recruiting --> Completed
Trial completion
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Tecentriq (atezolizumab) • gemcitabine • albumin-bound paclitaxel • delolimogene mupadenorepvec (LOAd703)
3ms
LOAd703-induced tumor microenvironment gene engineering in combination with atezolizumab in metastatic malignant melanoma: a phase I/II trial. (PubMed, Nat Commun)
The small sample size and single arm design limits effect interpretation but the data shows promise for continued clinical investigation. Study registration: NCT04123470.
P1/2 data • Journal • PD(L)-1 Biomarker • IO biomarker
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CD40LG (CD40 ligand)
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Tecentriq (atezolizumab) • delolimogene mupadenorepvec (LOAd703)
4ms
BMP-7 Treatment Ameliorates PTEN-Akt Mediated Apoptosis and Adverse Cardiac Remodeling in Ponatinib-Induced Cardiotoxicity. (PubMed, Pharmaceuticals (Basel))
These results suggest that BMP-7 might inhibit PON-induced cardiotoxicity. Furthermore, our findings pave the way for future translational studies with BMP-7, which can demonstrate the therapeutic potential of BMP-7 in a clinical setting.
Journal • IO biomarker
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PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3)
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Iclusig (ponatinib)
6ms
SARCOME13: Mifamurtide Combined With Post-operative Chemotherapy for Newly Diagnosed High Risk Osteosarcoma Patients (clinicaltrials.gov)
P2, N=60, Active, not recruiting, UNICANCER | Trial primary completion date: Sep 2025 --> Dec 2025
Trial primary completion date
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doxorubicin hydrochloride • Mepact (mifamurtide)
8ms
Micros: Tumor Microenvironment in Patients With Localized Osteosarcoma Treated With Mifamurtide: a Translational Study (clinicaltrials.gov)
P=N/A, N=80, Completed, Istituto Ortopedico Rizzoli | Trial completion date: Jun 2025 --> Oct 2024 | Trial primary completion date: Jun 2025 --> Oct 2024 | Recruiting --> Completed
Trial completion • Trial completion date • Trial primary completion date
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PD-L1 (Programmed death ligand 1)
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Mepact (mifamurtide)
8ms
The benefits of combining an immunomodulator with a chemotherapy agent in chondrosarcoma-a proof of concept with mifamurtide. (PubMed, Med Oncol)
These results highlight the importance of TAMs in modulating treatment response. This study provides a preclinical proof of concept for the efficacy of combining mifamurtide with doxorubicin in managing chondrosarcoma, highlighting the potential of immunomodulator and chemotherapy co-treatment in improving treatment outcomes.
Journal
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TLR4 (Toll Like Receptor 4)
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doxorubicin hydrochloride • Mepact (mifamurtide)
9ms
Is There a Role for Mifamurtide in Nonmetastatic High-Grade Osteosarcoma? Results From the Italian Sarcoma Group (ISG/OS-2) and Spanish Sarcoma Group (GEIS-33) Trials. (PubMed, J Clin Oncol)
In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery.
Journal
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ABCB1 (ATP Binding Cassette Subfamily B Member 1)
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cisplatin • doxorubicin hydrochloride • ifosfamide • methotrexate • Mepact (mifamurtide)