The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
Richard G Pestell - One of the best experts on this subject based on the ideXlab platform.
-
abstract pd4 04 Leronlimab a humanized monoclonal antibody to ccr5 restrains breast cancer metastasis and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2020Co-Authors: Richard G Pestell, Xuanmao Jiao, Massimo Cristofanilli, Min WangAbstract:Purpose of the study. To define the role of CCR5 in metastasis of breast cancer cells using a humanized monoclonal antibody to CCR5 (Leronlimab). CCR5, is a G protein coupled receptor that is normally expressed on immune cells. CCR5 expression is increase selectively in adult and pediatric malignancies including breast cancer (BCa), prostate cancer, pancreatic cancer, colon cancer, melanoma). In studies of >2,200 patients with breast CCR5 was overexpressed in >50% of human BCa, primarily in triple negative BCa (TNBC), correlating with poor outcome. Small molecule CCR5 inhibitors block breast and prostate cancer metastasis, but have known serious adverse events. Expression of CCR5 has been linked to both tumor immune heterogeneity and canonical check point inhibitor responses. CCR5 is activated by diverse ligands identified in the tumor microenvironment (CXCL13 (BCA-1), CCL3 (MIP1α), CCL3L1, CCL4 (MP-1β), CCL5 (RANTES), CCL8 (MCP2), CCL11 (Eotaxin), CCL13 (MCP-4), CCL16 (HCC-4). CCR5+ BCa epithelial cells have characteristics of cancer stem cells, initiating tumors and metastasizing in mice. CCR5 reintroduction into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used in treatment of >750 patients with HIV, and met its primary endpoints in a phase III pivotal study for HIV, without significant adverse events reported. A CCR5 targeted cancer clinical trials (phase 1) using a small molecule inhibitor with the check point inhibitor Pembrolizumab opened to accrual in late 2018 NCT03274804. Results. Leronlimab augmented BCa cell killing by DNA damage inducing agents. Leronlimab bound to CCR5 expressed in human breast cancer cell lines, abrogated CCL5 induced Ca+2 flux, blocked 3-d matrigel invasion and blocked metastasis of MDA-MB-231 cells in murine xenografts. At 7 weeks, metastatic BCa tumor burden was reduced >98% by Leronlimab. CCR5 was identified on patients9 circulating tumor cells (CTC). Based on these studies a phase 1b/2 clinical trial was approved for Leronlimab and carboplatin treatment of metastatic TNBC (NCT03838367) and granted fast track designation in May 2019. The trial monitors CTC in response to Leronlimab and progression free survival, Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular metastasis with a clinical trial currently accruing. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy. Citation Format: Richard G Pestell, Massimo Cristofanilli, Hallgeir Rui, Xuanmao Jiao, Min Wang. Leronlimab, a humanized monoclonal antibody to CCR5, restrains breast cancer metastasis and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-04.
-
Cytokine CCL5 and receptor CCR5 axis in glioblastoma multiforme
Radiology and Oncology, 2019Co-Authors: Miha Koprivnikar Kranjc, Metka Novak, Richard G PestellAbstract:: Background Glioblastoma is the most frequent and aggressive brain tumour in humans with median survival from 12 to 15 months after the diagnosis. This is mostly due to therapy resistant glioblastoma stem cells in addition to intertumour heterogeneity that is due to infiltration of a plethora of host cells. Besides endothelial cells, mesenchymal stem cells and their differentiated progenies, immune cells of various differentiation states, including monocytes, comprise resident, brain tumour microenvironment. There are compelling evidence for CCL5/CCR5 in the invasive and metastatic behaviour of many cancer types. CCR5, a G-protein coupled receptor, known to function as an essential co-receptor for HIV entry, is now known to participate in driving tumour heterogeneity, the formation of cancer stem cells and the promotion of cancer invasion and metastasis. Clinical trials have recently opened targeting CCR5 using a humanized monoclonal antibody (Leronlimab) for metastatic triple negative breast cancer (TNBC) or a small molecule inhibitor (maraviroc) for metastatic colon cancer. There are important CCL5 and CCR5 structure and signalling mechanisms in glioblastoma. In addition, the CCL5/CCR5 axis directs infiltration and interactions with monocytes/macrophages and mesenchymal stem cells, comprising glioblastoma stem cell niches. Conclusions CCR5 is highly expressed in glioblastoma and is associated with poor prognosis of patients. CCL5/CCR5 is suggested to be an excellent new target for glioblastoma therapy. The molecular mechanisms, by which chemoattractant and receptor respond within the complex tissue microenvironment to promote cancer stem cells and tumour heterogeneity, should be considered in forthcoming studies.
-
Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology.
Cancer Research, 2019Co-Authors: Xuanmao Jiao, Omar Nawab, Tejal Patel, Andrew V. Kossenkov, Niels Halama, Dirk Jaeger, Richard G PestellAbstract:Experiments of nature have revealed the peculiar importance of the G-protein–coupled receptor, C-C chemokine receptor type 5 (CCR5), in human disease since ancient times. The resurgence of interest in heterotypic signals in the onset and progression of tumorigenesis has led to the current focus on CCR5 as an exciting new therapeutic target for metastatic cancer with clinical trials now targeting breast and colon cancer. The eutopic expression of CCR5 activates calcium signaling and thereby augments regulatory T cell (Treg) differentiation and migration to sites of inflammation. The misexpression of CCR5 in epithelial cells, induced upon oncogenic transformation, hijacks this migratory phenotype. CCR5 reexpression augments resistance to DNA-damaging agents and is sufficient to induce cancer metastasis and “stemness”. Recent studies suggest important cross-talk between CCR5 signaling and immune checkpoint function. Because CCR5 on Tregs serves as the coreceptor for human immunodeficiency virus (HIV) entry, CCR5-targeted therapeutics used in HIV, [small molecules (maraviroc and vicriviroc) and a humanized mAb (Leronlimab)], are now being repositioned in clinical trials as cancer therapeutics. As CCR5 is expressed on a broad array of tumors, the opportunity for therapeutic repositioning and the rationale for combination therapy approaches are reviewed herein.
-
abstract 2009 Leronlimab a humanized monoclonal antibody to ccr5 blocks breast cancer cellular invasion and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2019Co-Authors: Xuanmao Jiao, Min Wang, Richard G PestellAbstract:Purpose of the study. To assess binding and functional interaction of the humanized monoclonal antibody to CCR5 (Leronlimab) with human breast cancer cell lines. The G protein coupled receptor CCR5, is normally expressed on a subset of T cells and serves as a co-receptor for HIV infection. During malignant transformation CCR5 expression is known to increase in a number of cancers (breast cancer (BCa), prostate cancer, colon cancer, melanoma). CCR5 targeted cancer clinical trials using small molecular inhibitors opened to accrual in late 2018. CCR5 is expressed in >50% of human BCa, primarily in triple negative BCa. Its expression in human BCa correlates with poor outcome and CCR5+ BCa epithelial cells have characteristics of cancer stem cells, forming mammospheres and initiating tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used for treatment of >550 patients HIV, including meeting its primary endpoints in a phase III study, without significant adverse events reported. Results. Leronlimab bound to CCR5 expressed in human breast cancer cell lines with 98% efficiency. Leronlimab abrogated CCL5 induced Ca+2 flux and blocked 3-d matrigel invasion of MDA-MB-231 cells. Leronlimab also augmented cell killing by DNA damage inducing agents Doxorubicin. Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and augmenting cell killing by DNA damage inducing chemotherapies. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy and radiation. Citation Format: Xuanmao Jiao, Min Wang, Richard G. Pestell. Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular invasion and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2009.
Min Wang - One of the best experts on this subject based on the ideXlab platform.
-
abstract pd4 04 Leronlimab a humanized monoclonal antibody to ccr5 restrains breast cancer metastasis and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2020Co-Authors: Richard G Pestell, Xuanmao Jiao, Massimo Cristofanilli, Min WangAbstract:Purpose of the study. To define the role of CCR5 in metastasis of breast cancer cells using a humanized monoclonal antibody to CCR5 (Leronlimab). CCR5, is a G protein coupled receptor that is normally expressed on immune cells. CCR5 expression is increase selectively in adult and pediatric malignancies including breast cancer (BCa), prostate cancer, pancreatic cancer, colon cancer, melanoma). In studies of >2,200 patients with breast CCR5 was overexpressed in >50% of human BCa, primarily in triple negative BCa (TNBC), correlating with poor outcome. Small molecule CCR5 inhibitors block breast and prostate cancer metastasis, but have known serious adverse events. Expression of CCR5 has been linked to both tumor immune heterogeneity and canonical check point inhibitor responses. CCR5 is activated by diverse ligands identified in the tumor microenvironment (CXCL13 (BCA-1), CCL3 (MIP1α), CCL3L1, CCL4 (MP-1β), CCL5 (RANTES), CCL8 (MCP2), CCL11 (Eotaxin), CCL13 (MCP-4), CCL16 (HCC-4). CCR5+ BCa epithelial cells have characteristics of cancer stem cells, initiating tumors and metastasizing in mice. CCR5 reintroduction into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used in treatment of >750 patients with HIV, and met its primary endpoints in a phase III pivotal study for HIV, without significant adverse events reported. A CCR5 targeted cancer clinical trials (phase 1) using a small molecule inhibitor with the check point inhibitor Pembrolizumab opened to accrual in late 2018 NCT03274804. Results. Leronlimab augmented BCa cell killing by DNA damage inducing agents. Leronlimab bound to CCR5 expressed in human breast cancer cell lines, abrogated CCL5 induced Ca+2 flux, blocked 3-d matrigel invasion and blocked metastasis of MDA-MB-231 cells in murine xenografts. At 7 weeks, metastatic BCa tumor burden was reduced >98% by Leronlimab. CCR5 was identified on patients9 circulating tumor cells (CTC). Based on these studies a phase 1b/2 clinical trial was approved for Leronlimab and carboplatin treatment of metastatic TNBC (NCT03838367) and granted fast track designation in May 2019. The trial monitors CTC in response to Leronlimab and progression free survival, Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular metastasis with a clinical trial currently accruing. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy. Citation Format: Richard G Pestell, Massimo Cristofanilli, Hallgeir Rui, Xuanmao Jiao, Min Wang. Leronlimab, a humanized monoclonal antibody to CCR5, restrains breast cancer metastasis and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-04.
-
abstract 2009 Leronlimab a humanized monoclonal antibody to ccr5 blocks breast cancer cellular invasion and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2019Co-Authors: Xuanmao Jiao, Min Wang, Richard G PestellAbstract:Purpose of the study. To assess binding and functional interaction of the humanized monoclonal antibody to CCR5 (Leronlimab) with human breast cancer cell lines. The G protein coupled receptor CCR5, is normally expressed on a subset of T cells and serves as a co-receptor for HIV infection. During malignant transformation CCR5 expression is known to increase in a number of cancers (breast cancer (BCa), prostate cancer, colon cancer, melanoma). CCR5 targeted cancer clinical trials using small molecular inhibitors opened to accrual in late 2018. CCR5 is expressed in >50% of human BCa, primarily in triple negative BCa. Its expression in human BCa correlates with poor outcome and CCR5+ BCa epithelial cells have characteristics of cancer stem cells, forming mammospheres and initiating tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used for treatment of >550 patients HIV, including meeting its primary endpoints in a phase III study, without significant adverse events reported. Results. Leronlimab bound to CCR5 expressed in human breast cancer cell lines with 98% efficiency. Leronlimab abrogated CCL5 induced Ca+2 flux and blocked 3-d matrigel invasion of MDA-MB-231 cells. Leronlimab also augmented cell killing by DNA damage inducing agents Doxorubicin. Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and augmenting cell killing by DNA damage inducing chemotherapies. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy and radiation. Citation Format: Xuanmao Jiao, Min Wang, Richard G. Pestell. Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular invasion and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2009.
Xuanmao Jiao - One of the best experts on this subject based on the ideXlab platform.
-
abstract pd4 04 Leronlimab a humanized monoclonal antibody to ccr5 restrains breast cancer metastasis and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2020Co-Authors: Richard G Pestell, Xuanmao Jiao, Massimo Cristofanilli, Min WangAbstract:Purpose of the study. To define the role of CCR5 in metastasis of breast cancer cells using a humanized monoclonal antibody to CCR5 (Leronlimab). CCR5, is a G protein coupled receptor that is normally expressed on immune cells. CCR5 expression is increase selectively in adult and pediatric malignancies including breast cancer (BCa), prostate cancer, pancreatic cancer, colon cancer, melanoma). In studies of >2,200 patients with breast CCR5 was overexpressed in >50% of human BCa, primarily in triple negative BCa (TNBC), correlating with poor outcome. Small molecule CCR5 inhibitors block breast and prostate cancer metastasis, but have known serious adverse events. Expression of CCR5 has been linked to both tumor immune heterogeneity and canonical check point inhibitor responses. CCR5 is activated by diverse ligands identified in the tumor microenvironment (CXCL13 (BCA-1), CCL3 (MIP1α), CCL3L1, CCL4 (MP-1β), CCL5 (RANTES), CCL8 (MCP2), CCL11 (Eotaxin), CCL13 (MCP-4), CCL16 (HCC-4). CCR5+ BCa epithelial cells have characteristics of cancer stem cells, initiating tumors and metastasizing in mice. CCR5 reintroduction into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used in treatment of >750 patients with HIV, and met its primary endpoints in a phase III pivotal study for HIV, without significant adverse events reported. A CCR5 targeted cancer clinical trials (phase 1) using a small molecule inhibitor with the check point inhibitor Pembrolizumab opened to accrual in late 2018 NCT03274804. Results. Leronlimab augmented BCa cell killing by DNA damage inducing agents. Leronlimab bound to CCR5 expressed in human breast cancer cell lines, abrogated CCL5 induced Ca+2 flux, blocked 3-d matrigel invasion and blocked metastasis of MDA-MB-231 cells in murine xenografts. At 7 weeks, metastatic BCa tumor burden was reduced >98% by Leronlimab. CCR5 was identified on patients9 circulating tumor cells (CTC). Based on these studies a phase 1b/2 clinical trial was approved for Leronlimab and carboplatin treatment of metastatic TNBC (NCT03838367) and granted fast track designation in May 2019. The trial monitors CTC in response to Leronlimab and progression free survival, Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular metastasis with a clinical trial currently accruing. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy. Citation Format: Richard G Pestell, Massimo Cristofanilli, Hallgeir Rui, Xuanmao Jiao, Min Wang. Leronlimab, a humanized monoclonal antibody to CCR5, restrains breast cancer metastasis and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-04.
-
Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology.
Cancer Research, 2019Co-Authors: Xuanmao Jiao, Omar Nawab, Tejal Patel, Andrew V. Kossenkov, Niels Halama, Dirk Jaeger, Richard G PestellAbstract:Experiments of nature have revealed the peculiar importance of the G-protein–coupled receptor, C-C chemokine receptor type 5 (CCR5), in human disease since ancient times. The resurgence of interest in heterotypic signals in the onset and progression of tumorigenesis has led to the current focus on CCR5 as an exciting new therapeutic target for metastatic cancer with clinical trials now targeting breast and colon cancer. The eutopic expression of CCR5 activates calcium signaling and thereby augments regulatory T cell (Treg) differentiation and migration to sites of inflammation. The misexpression of CCR5 in epithelial cells, induced upon oncogenic transformation, hijacks this migratory phenotype. CCR5 reexpression augments resistance to DNA-damaging agents and is sufficient to induce cancer metastasis and “stemness”. Recent studies suggest important cross-talk between CCR5 signaling and immune checkpoint function. Because CCR5 on Tregs serves as the coreceptor for human immunodeficiency virus (HIV) entry, CCR5-targeted therapeutics used in HIV, [small molecules (maraviroc and vicriviroc) and a humanized mAb (Leronlimab)], are now being repositioned in clinical trials as cancer therapeutics. As CCR5 is expressed on a broad array of tumors, the opportunity for therapeutic repositioning and the rationale for combination therapy approaches are reviewed herein.
-
abstract 2009 Leronlimab a humanized monoclonal antibody to ccr5 blocks breast cancer cellular invasion and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2019Co-Authors: Xuanmao Jiao, Min Wang, Richard G PestellAbstract:Purpose of the study. To assess binding and functional interaction of the humanized monoclonal antibody to CCR5 (Leronlimab) with human breast cancer cell lines. The G protein coupled receptor CCR5, is normally expressed on a subset of T cells and serves as a co-receptor for HIV infection. During malignant transformation CCR5 expression is known to increase in a number of cancers (breast cancer (BCa), prostate cancer, colon cancer, melanoma). CCR5 targeted cancer clinical trials using small molecular inhibitors opened to accrual in late 2018. CCR5 is expressed in >50% of human BCa, primarily in triple negative BCa. Its expression in human BCa correlates with poor outcome and CCR5+ BCa epithelial cells have characteristics of cancer stem cells, forming mammospheres and initiating tumors with >60-fold greater efficiency in mice. Reintroduction of CCR5 expression into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used for treatment of >550 patients HIV, including meeting its primary endpoints in a phase III study, without significant adverse events reported. Results. Leronlimab bound to CCR5 expressed in human breast cancer cell lines with 98% efficiency. Leronlimab abrogated CCL5 induced Ca+2 flux and blocked 3-d matrigel invasion of MDA-MB-231 cells. Leronlimab also augmented cell killing by DNA damage inducing agents Doxorubicin. Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and augmenting cell killing by DNA damage inducing chemotherapies. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy and radiation. Citation Format: Xuanmao Jiao, Min Wang, Richard G. Pestell. Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular invasion and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2009.
Massimo Cristofanilli - One of the best experts on this subject based on the ideXlab platform.
-
abstract pd4 04 Leronlimab a humanized monoclonal antibody to ccr5 restrains breast cancer metastasis and enhances cell death induced by dna damaging chemotherapies
Cancer Research, 2020Co-Authors: Richard G Pestell, Xuanmao Jiao, Massimo Cristofanilli, Min WangAbstract:Purpose of the study. To define the role of CCR5 in metastasis of breast cancer cells using a humanized monoclonal antibody to CCR5 (Leronlimab). CCR5, is a G protein coupled receptor that is normally expressed on immune cells. CCR5 expression is increase selectively in adult and pediatric malignancies including breast cancer (BCa), prostate cancer, pancreatic cancer, colon cancer, melanoma). In studies of >2,200 patients with breast CCR5 was overexpressed in >50% of human BCa, primarily in triple negative BCa (TNBC), correlating with poor outcome. Small molecule CCR5 inhibitors block breast and prostate cancer metastasis, but have known serious adverse events. Expression of CCR5 has been linked to both tumor immune heterogeneity and canonical check point inhibitor responses. CCR5 is activated by diverse ligands identified in the tumor microenvironment (CXCL13 (BCA-1), CCL3 (MIP1α), CCL3L1, CCL4 (MP-1β), CCL5 (RANTES), CCL8 (MCP2), CCL11 (Eotaxin), CCL13 (MCP-4), CCL16 (HCC-4). CCR5+ BCa epithelial cells have characteristics of cancer stem cells, initiating tumors and metastasizing in mice. CCR5 reintroduction into CCR5 negative BCa cells promotes tumor metastases and induces DNA repair gene expression and activity. The CCR5 inhibitor Leronlimab has been used in treatment of >750 patients with HIV, and met its primary endpoints in a phase III pivotal study for HIV, without significant adverse events reported. A CCR5 targeted cancer clinical trials (phase 1) using a small molecule inhibitor with the check point inhibitor Pembrolizumab opened to accrual in late 2018 NCT03274804. Results. Leronlimab augmented BCa cell killing by DNA damage inducing agents. Leronlimab bound to CCR5 expressed in human breast cancer cell lines, abrogated CCL5 induced Ca+2 flux, blocked 3-d matrigel invasion and blocked metastasis of MDA-MB-231 cells in murine xenografts. At 7 weeks, metastatic BCa tumor burden was reduced >98% by Leronlimab. CCR5 was identified on patients9 circulating tumor cells (CTC). Based on these studies a phase 1b/2 clinical trial was approved for Leronlimab and carboplatin treatment of metastatic TNBC (NCT03838367) and granted fast track designation in May 2019. The trial monitors CTC in response to Leronlimab and progression free survival, Conclusions. Leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular metastasis with a clinical trial currently accruing. As CCR5 augments DNA repair and is expressed selectively on cancerous but not normal breast epithelial cells, Leronlimab may enhance the tumor specific activities of DDR-based treatments, allowing a reduction in dose of standard chemotherapy. Citation Format: Richard G Pestell, Massimo Cristofanilli, Hallgeir Rui, Xuanmao Jiao, Min Wang. Leronlimab, a humanized monoclonal antibody to CCR5, restrains breast cancer metastasis and enhances cell death induced by DNA damaging chemotherapies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD4-04.
Raphael L. Landovitz - One of the best experts on this subject based on the ideXlab platform.
-
Advances in Long-Acting Agents for the Treatment of HIV Infection
Drugs, 2020Co-Authors: Aadia I. Rana, Jose R. Castillo-mancilla, Karen T. Tashima, Raphael L. LandovitzAbstract:Long-acting antiretroviral therapy holds the promise of new options for human immunodeficiency virus (HIV) treatment beyond the current paradigm of daily oral pills. Of particular interest is their potential role in addressing challenges with adherence to oral therapy and treatment fatigue. Similar to other conditions where long-acting formulations have proven effective such as contraception and mental health, long-acting antiretroviral therapy could provide additional treatment choices to people with HIV. This review provides an outline of the current landscape of long-acting antiretroviral therapy for HIV treatment, both approved and under development, including cabotegravir, rilpivirine, Leronlimab, islatravir, albuvirtide, GS-6207, and broadly neutralizaing antibodies. However, there are a number of research gaps for long-acting antiretroviral therapy including issues regarding resistance and understudied populations, and this review highlights some of the challenges that will need to be addressed for clinical implementation of these novel treatment modalities.