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Posted On: 07/19/2024 3:51:51 PM
Post# of 148870
The following was posted on 12/11/2023 by CGC (thank you CGC!)
and I think is very helpful (the video link at the bottom is also worth a look):
Leronlimab: Next Generation Monoclonal Antibody Therapy in Cancer Indication
How it Works: Leronlimab (PRO 140) is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH.
Leronlimab inhibits angiogenesis by downregulating VEGF, anti-trafficking of tumor cells, increase in tumor fighting NKT cells, debases DNA repair, stops the recruitment of Tregs to tumor sites (Tregs promote tumor immunity), downregulates IL-13 a tumor protectant and IL-4 (IL-4 promotes tumor immunity), upregulates IFN-gamma promoting tumor cell death and downregulates PD-L1. Downregulates CDK2/4/6, cyclin D1, cyclin E, and PCNA which are implicated in tumor cell growth. Upregulates p27 and p53 which are both tumor suppressors.
In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, & tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory & animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn has conducting several human clinical trials to establish proof of concept and efficacy in patients with cancer.
Taken Along with Current Treatment: The study treatment, Leronlimab, is a once per week subcutaneous injection. It can be used along with one’s current cancer treatment.
Major possible benefits:
o Reducing metastasis: as CCR5/CCL5 is the axis that white blood cells use for chemotaxis
o Restoring Tumor microenvironment: as blocking CCR5 can repolarize White Blood Cells
o In CCR5 over-expressing cancers: CCR5 over-expression seems to play a role in chemo and therapeutic resistance; Blocking CCR5 seems to increase effectiveness of therapies
Impeccable Safety Profile: Lack of SAEs, well tolerated, in more than one thousand patients over five years, in a population as fragile as HIV patients. The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial. Cancer trials include a Phase 2 compassionate use study in metastatic triple-negative breast cancer (being granted Fast Track designation in May 2019) and a Phase 2 basket study on patients with CCR5 locally advanced or metastatic sold tumor.
Rapid Results:
o Trials are indicating drops of CTC and reduction of EMT cells and putative metastic cells.
o Leronlimab may help in advanced TNBC. Blocking CCR5 is being found to possibly reduce metastasis and reduce the ability of tumor cells to maintain the micro-environment that enables them to avoid other chemotherapies and the body's immune system.
Main Resources:
• Safety, efficacy, and clinical outcomes of the anti-CCR5 inhibitor (Leronlimab): A pooled analysis of three clinical trials in patients with mTNBC.
https://ascopubs.org/doi/abs/10.1200/JCO.2022...ppl.e13062
• Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy. Conclusion: strong preclinical evidence to both prevent and reduce established breast cancer metastasis. https://breast-cancer-research.biomedcentral....21-01391-1
• Recent Advances Targeting CCR5 for Cancer and its Role in Immuno-Oncology. https://aacrjournals.org/cancerres/article/79...er-and-Its
• A review of antibody-based therapeutics targeting G protein-coupled receptors. https://www.tandfonline.com/doi/full/10.1080/...20.1745770
• The CCL5/CCR5 Axis in Cancer Progression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407580/
• CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...po=2.50000
• CCR5 in Breast Cancer
https://encyclopedia.pub/entry/49484
• The Role and Therapeutic Targeting of CCR5 in Breast Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...0therapies.
• An agent-based model of triple-negative breast cancer: the interplay between chemokine receptor CCR5 expression, cancer stem cells, hypoxia
https://bmcsystbiol.biomedcentral.com/article...017-0445-x
• CCR5 and Cancer: Cytodyn Inc.
https://www.cytodyn.com/our-science/ccr5-and-cancer; https://www.cytodyn.com/pipeline/cancer
Video: Mechanism of Action Animation for leronlimab in Immuno-Oncology: https://www.youtube.com/watch?v=uxkc6Ql1C-U
Advisory Board: https://www.cytodyn.com/scientific-advisory-board
and I think is very helpful (the video link at the bottom is also worth a look):
Leronlimab: Next Generation Monoclonal Antibody Therapy in Cancer Indication
How it Works: Leronlimab (PRO 140) is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH.
Leronlimab inhibits angiogenesis by downregulating VEGF, anti-trafficking of tumor cells, increase in tumor fighting NKT cells, debases DNA repair, stops the recruitment of Tregs to tumor sites (Tregs promote tumor immunity), downregulates IL-13 a tumor protectant and IL-4 (IL-4 promotes tumor immunity), upregulates IFN-gamma promoting tumor cell death and downregulates PD-L1. Downregulates CDK2/4/6, cyclin D1, cyclin E, and PCNA which are implicated in tumor cell growth. Upregulates p27 and p53 which are both tumor suppressors.
In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, & tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory & animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn has conducting several human clinical trials to establish proof of concept and efficacy in patients with cancer.
Taken Along with Current Treatment: The study treatment, Leronlimab, is a once per week subcutaneous injection. It can be used along with one’s current cancer treatment.
Major possible benefits:
o Reducing metastasis: as CCR5/CCL5 is the axis that white blood cells use for chemotaxis
o Restoring Tumor microenvironment: as blocking CCR5 can repolarize White Blood Cells
o In CCR5 over-expressing cancers: CCR5 over-expression seems to play a role in chemo and therapeutic resistance; Blocking CCR5 seems to increase effectiveness of therapies
Impeccable Safety Profile: Lack of SAEs, well tolerated, in more than one thousand patients over five years, in a population as fragile as HIV patients. The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial. Cancer trials include a Phase 2 compassionate use study in metastatic triple-negative breast cancer (being granted Fast Track designation in May 2019) and a Phase 2 basket study on patients with CCR5 locally advanced or metastatic sold tumor.
Rapid Results:
o Trials are indicating drops of CTC and reduction of EMT cells and putative metastic cells.
o Leronlimab may help in advanced TNBC. Blocking CCR5 is being found to possibly reduce metastasis and reduce the ability of tumor cells to maintain the micro-environment that enables them to avoid other chemotherapies and the body's immune system.
Main Resources:
• Safety, efficacy, and clinical outcomes of the anti-CCR5 inhibitor (Leronlimab): A pooled analysis of three clinical trials in patients with mTNBC.
https://ascopubs.org/doi/abs/10.1200/JCO.2022...ppl.e13062
• Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy. Conclusion: strong preclinical evidence to both prevent and reduce established breast cancer metastasis. https://breast-cancer-research.biomedcentral....21-01391-1
• Recent Advances Targeting CCR5 for Cancer and its Role in Immuno-Oncology. https://aacrjournals.org/cancerres/article/79...er-and-Its
• A review of antibody-based therapeutics targeting G protein-coupled receptors. https://www.tandfonline.com/doi/full/10.1080/...20.1745770
• The CCL5/CCR5 Axis in Cancer Progression
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407580/
• CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...po=2.50000
• CCR5 in Breast Cancer
https://encyclopedia.pub/entry/49484
• The Role and Therapeutic Targeting of CCR5 in Breast Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC...0therapies.
• An agent-based model of triple-negative breast cancer: the interplay between chemokine receptor CCR5 expression, cancer stem cells, hypoxia
https://bmcsystbiol.biomedcentral.com/article...017-0445-x
• CCR5 and Cancer: Cytodyn Inc.
https://www.cytodyn.com/our-science/ccr5-and-cancer; https://www.cytodyn.com/pipeline/cancer
Video: Mechanism of Action Animation for leronlimab in Immuno-Oncology: https://www.youtube.com/watch?v=uxkc6Ql1C-U
Advisory Board: https://www.cytodyn.com/scientific-advisory-board
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