EIND: Information to Submit to Doctors
I ran across some new information for the person I'm trying to convince to get an EIND for breast cancer. I also added the new posters from our April presentations. Her specific breast cancer is progesterone negative, estrogen positive, HER2 positive. The new information pertains to any estrogen positive or progesterone negative cancer. Problems arise when our old friends the PI3K/AKT/mTOR and MAPK/ERK pathways are highly activated. In estrogen positive the estrogen can boost both pathways along with CCR5 itself doing so. Those pathways in return can increase estrogen reducing the effectiveness of any inhibitor being used. With progesterone its receptors decrease over time when a progesterone booster is being used leading to activation of the pathways. With both PI3K/AKT/mTOR and MAPK/ERK they drive tumor growth all on its own. Leronlimab of course downregulates both pathways restoring the effectiveness of those treatments.
I am appending the new information to the information in the old pinned post so it can be pinned in its place.
Here is a list of publications that I printed out for someone possibly seeking an EIND for breast cancer to give to their doctor. I also printed out the list of links and a cover letter for contacting Cytodyn. It's not TNBC so she's not eligible for the current or upcoming trial.
Contact Information
Website - www.cytodyn.com
Phone - 360-980-8524
Email - info@cytodyn.com
Cytodyn welcomes all requests for the use of it's drug leronlimab under the FDA's Emergency Investigational New Drug Program. The preferred method of contact by physicians or patients is through Cytodyn's email address. Cytodyn will respond with more information about the drug and the steps to take to initiate the EIND process.
Online Links to Publications
Leronlimab is associated with long-term survival in metastatic TNBC: Enhancing PD-L1 expression, ICI response, and modulates T cell exhaustion
Abstract - https://aacrjournals.org/cancerimmunolres/art...-with-long
Poster - https://d1io3yog0oux5.cloudfront.net/_976f96f...evised.pdf
Prolonged survival following PD-L1/PD-1 immune checkpoint inhibitor therapy after leronlimab induced PD-L1 upregulation on cancer-associated macrophage-like cells and circulating tumor cells in patients with metastatic or locally advanced triple-negative breast cancer
Abstract - https://aacrjournals.org/clincancerres/articl...llowing-PD
Poster - https://d1io3yog0oux5.cloudfront.net/_fb000f7..._FINAL.pdf
Long Term Survival with Leronlimab Treatment in Patients with Metastatic Triple-Negative Breast Cancer (mTNBC)
Poster - https://d1io3yog0oux5.cloudfront.net/_976f96f...28h%29.pdf
Leronlimab induces PD-L1 expression and is associated with long‑term survival with an ICI in PD-L1 low metastatic TNBC
Abstract (for April 19, 2026 presentation) - https://www.abstractsonline.com/pp8/#!/21436/...ation/9742
Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy
Publication - https://link.springer.com/article/10.1186/s13058-021-01391-1
Leronlimab induces PD-L1 expression and is associated with long-term survival with an ICI in PD-L1 low metastatic TNBC
https://d1io3yog0oux5.cloudfront.net/_8fabbae...P+3-21.pdf
Leronlimab in combination with trifluridine/tipiracil (TAS-102) plus bevacizumab for patients with
refractory metastatic colorectal cancer (mCRC): The phase 2 CLOVER study
https://d1io3yog0oux5.cloudfront.net/_bda4625...026_V6.pdf
The Role and Therapeutic Targeting of CCR5 in Breast Cancer
Publication - https://pdfs.semanticscholar.org/c499/b3b8f8d...32aa89.pdf
The CCL5/CCR5 Axis in Cancer Progression
Publication - https://www.mdpi.com/2072-6694/12/7/1765
Progesterone +. Estrogen+, specific information
Leronlimab a humanized monoclonal antibody binds CCR5, blocking binding of it's C-C chemokine ligands (preferentially binding CCL-4 and CCL-5). Leronlimab downregulates both the PI3K/AKT/mTOR and MAPK/ERK pathways.
CCL5/CCR5 axis in human diseases and related treatments
"CCL5/CCR5 axis focus on influencing the cell cycle of tumor cells through abnormally activating NF-κB, mTOR and PI3K/AKT signaling pathways. At the molecular level, the cell division-related genes like cyclin D1, c-Myc and Dad-1 are overexpressed at tumor cell surface. They cooperate with each other to strengthen the mitogenesis. Furthermore, mTOR-mediated glycolysis and ATP production provide sufficient energy for the growth of tumor cells. In this process, CCL5/CCR5 combination triggers mTOR signaling continuously for cell proliferation."
https://pmc.ncbi.nlm.nih.gov/articles/PMC8423937/
The Inflammatory Chemokine CCL5 and Cancer Progression
"More specifically, CCL5 contributes to the activation of the αvβ3 integrin and to cell migration through PI3K/Akt, which in turn activates IKKalpha/beta and NF-κB. NF-κB activation also can elevate the secretion of MMP-9 or promote invasion by increasing the secretion of both MMP-2 and -9 and by activating the ERK and Rac signaling [27]. CCL5 induces migration also by upregulating the activities of MMP-9 through STAT3 [28]. In other instances CCL5/CCR5 acts via MEK, ERK, and then NF-κB, resulting in the activations of αvβ3 integrin and contributing to cell migration.
Chemokines, by activating the tyrosine kinase receptors, the Jak-STAT, or the MAPK/ERK signaling pathway, also promote tumor cell proliferation. Exogenous CCL5 stimulates cell proliferation by inducing the mTOR pathway, leading to a rapid upregulation of cyclin D1, c-Myc, and Dad-1 expression. An additional mechanism based on the CCL5-CCR5 interaction can lead to increased cell proliferation: increased glucose uptake, increased ATP production, and enhanced glycolysis, associated with extracellular acidification"
https://onlinelibrary.wiley.com/doi/10.1155/2014/292376
====================================================================================================
Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies
"Endocrine therapy combined with mTOR inhibitors
The PI3K–AKT–mTOR pathway has also been implicated to play a crucial role in tumor proliferation and progression. Several studies showed that the upregulation of the PI3K–AKT–mTOR pathway interacts with the ER pathway and confers endocrine resistance... Another preclinical study showed that co-treatment with low concentrations of mTOR inhibitor RAD001 combining with either letrozole or fulvestrant could restore the response of the resistant cells with high Akt activity. In addition, it could also resensitize breast cancer cells that did not respond to letrozole or fulvestrant as a single agent"
https://pmc.ncbi.nlm.nih.gov/articles/PMC5558537/
The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer
"The MAPK/ERK pathway is one of the most classical intracellular signaling pathways which is involved in tumor progression and drug resistance. The activation of the MAPK/ERK signaling axis phosphorylates ER, increases the sensitivity of ER to estrogen, and thereby contributes to endocrine therapy resistance. In addition, it communicates with other signaling pathways and cooperates to promote the proliferation and migration of tumor cells."
https://pmc.ncbi.nlm.nih.gov/articles/PMC10611521/#s7
I ran across some new information for the person I'm trying to convince to get an EIND for breast cancer. I also added the new posters from our April presentations. Her specific breast cancer is progesterone negative, estrogen positive, HER2 positive. The new information pertains to any estrogen positive or progesterone negative cancer. Problems arise when our old friends the PI3K/AKT/mTOR and MAPK/ERK pathways are highly activated. In estrogen positive the estrogen can boost both pathways along with CCR5 itself doing so. Those pathways in return can increase estrogen reducing the effectiveness of any inhibitor being used. With progesterone its receptors decrease over time when a progesterone booster is being used leading to activation of the pathways. With both PI3K/AKT/mTOR and MAPK/ERK they drive tumor growth all on its own. Leronlimab of course downregulates both pathways restoring the effectiveness of those treatments.
I am appending the new information to the information in the old pinned post so it can be pinned in its place.
Here is a list of publications that I printed out for someone possibly seeking an EIND for breast cancer to give to their doctor. I also printed out the list of links and a cover letter for contacting Cytodyn. It's not TNBC so she's not eligible for the current or upcoming trial.
Contact Information
Website - www.cytodyn.com
Phone - 360-980-8524
Email - info@cytodyn.com
Cytodyn welcomes all requests for the use of it's drug leronlimab under the FDA's Emergency Investigational New Drug Program. The preferred method of contact by physicians or patients is through Cytodyn's email address. Cytodyn will respond with more information about the drug and the steps to take to initiate the EIND process.
Online Links to Publications
Leronlimab is associated with long-term survival in metastatic TNBC: Enhancing PD-L1 expression, ICI response, and modulates T cell exhaustion
Abstract - https://aacrjournals.org/cancerimmunolres/art...-with-long
Poster - https://d1io3yog0oux5.cloudfront.net/_976f96f...evised.pdf
Prolonged survival following PD-L1/PD-1 immune checkpoint inhibitor therapy after leronlimab induced PD-L1 upregulation on cancer-associated macrophage-like cells and circulating tumor cells in patients with metastatic or locally advanced triple-negative breast cancer
Abstract - https://aacrjournals.org/clincancerres/articl...llowing-PD
Poster - https://d1io3yog0oux5.cloudfront.net/_fb000f7..._FINAL.pdf
Long Term Survival with Leronlimab Treatment in Patients with Metastatic Triple-Negative Breast Cancer (mTNBC)
Poster - https://d1io3yog0oux5.cloudfront.net/_976f96f...28h%29.pdf
Leronlimab induces PD-L1 expression and is associated with long‑term survival with an ICI in PD-L1 low metastatic TNBC
Abstract (for April 19, 2026 presentation) - https://www.abstractsonline.com/pp8/#!/21436/...ation/9742
Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy
Publication - https://link.springer.com/article/10.1186/s13058-021-01391-1
Leronlimab induces PD-L1 expression and is associated with long-term survival with an ICI in PD-L1 low metastatic TNBC
https://d1io3yog0oux5.cloudfront.net/_8fabbae...P+3-21.pdf
Leronlimab in combination with trifluridine/tipiracil (TAS-102) plus bevacizumab for patients with
refractory metastatic colorectal cancer (mCRC): The phase 2 CLOVER study
https://d1io3yog0oux5.cloudfront.net/_bda4625...026_V6.pdf
The Role and Therapeutic Targeting of CCR5 in Breast Cancer
Publication - https://pdfs.semanticscholar.org/c499/b3b8f8d...32aa89.pdf
The CCL5/CCR5 Axis in Cancer Progression
Publication - https://www.mdpi.com/2072-6694/12/7/1765
Progesterone +. Estrogen+, specific information
Leronlimab a humanized monoclonal antibody binds CCR5, blocking binding of it's C-C chemokine ligands (preferentially binding CCL-4 and CCL-5). Leronlimab downregulates both the PI3K/AKT/mTOR and MAPK/ERK pathways.
CCL5/CCR5 axis in human diseases and related treatments
"CCL5/CCR5 axis focus on influencing the cell cycle of tumor cells through abnormally activating NF-κB, mTOR and PI3K/AKT signaling pathways. At the molecular level, the cell division-related genes like cyclin D1, c-Myc and Dad-1 are overexpressed at tumor cell surface. They cooperate with each other to strengthen the mitogenesis. Furthermore, mTOR-mediated glycolysis and ATP production provide sufficient energy for the growth of tumor cells. In this process, CCL5/CCR5 combination triggers mTOR signaling continuously for cell proliferation."
https://pmc.ncbi.nlm.nih.gov/articles/PMC8423937/
The Inflammatory Chemokine CCL5 and Cancer Progression
"More specifically, CCL5 contributes to the activation of the αvβ3 integrin and to cell migration through PI3K/Akt, which in turn activates IKKalpha/beta and NF-κB. NF-κB activation also can elevate the secretion of MMP-9 or promote invasion by increasing the secretion of both MMP-2 and -9 and by activating the ERK and Rac signaling [27]. CCL5 induces migration also by upregulating the activities of MMP-9 through STAT3 [28]. In other instances CCL5/CCR5 acts via MEK, ERK, and then NF-κB, resulting in the activations of αvβ3 integrin and contributing to cell migration.
Chemokines, by activating the tyrosine kinase receptors, the Jak-STAT, or the MAPK/ERK signaling pathway, also promote tumor cell proliferation. Exogenous CCL5 stimulates cell proliferation by inducing the mTOR pathway, leading to a rapid upregulation of cyclin D1, c-Myc, and Dad-1 expression. An additional mechanism based on the CCL5-CCR5 interaction can lead to increased cell proliferation: increased glucose uptake, increased ATP production, and enhanced glycolysis, associated with extracellular acidification"
https://onlinelibrary.wiley.com/doi/10.1155/2014/292376
====================================================================================================
Endocrine therapy resistance in breast cancer: current status, possible mechanisms and overcoming strategies
"Endocrine therapy combined with mTOR inhibitors
The PI3K–AKT–mTOR pathway has also been implicated to play a crucial role in tumor proliferation and progression. Several studies showed that the upregulation of the PI3K–AKT–mTOR pathway interacts with the ER pathway and confers endocrine resistance... Another preclinical study showed that co-treatment with low concentrations of mTOR inhibitor RAD001 combining with either letrozole or fulvestrant could restore the response of the resistant cells with high Akt activity. In addition, it could also resensitize breast cancer cells that did not respond to letrozole or fulvestrant as a single agent"
https://pmc.ncbi.nlm.nih.gov/articles/PMC5558537/
The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer
"The MAPK/ERK pathway is one of the most classical intracellular signaling pathways which is involved in tumor progression and drug resistance. The activation of the MAPK/ERK signaling axis phosphorylates ER, increases the sensitivity of ER to estrogen, and thereby contributes to endocrine therapy resistance. In addition, it communicates with other signaling pathways and cooperates to promote the proliferation and migration of tumor cells."
https://pmc.ncbi.nlm.nih.gov/articles/PMC10611521/#s7
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