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Posted On: 06/21/2022 2:41:18 AM
Post# of 148876
Great read from the patent application!
[0012] The present disclosure relates to the use of DNA damaging agents and leronlimab (PRO 140), or other anti-CCR5 agents, to treat or prevent cancer metastases and enhance the cell killing ability of the DNA damaging agents by selectively targeting the CCR5 receptor. The present disclosure relates to the use of DNA damaging agents and leronlimab (PRO 140), or other anti-CCR5 agents, to treat or prevent cancer metastases and reduce circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood following treatment, reduce CCR5 expression on cancer-associated cells after following treatment, decrease volume in tumor size following treatment. The present disclosure may be used to treat or prevent subjects with cancer and, particularly, subjects with metastatic CCR5+ cancer.
[0096] It has been found that leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and tumor metastasis, 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 DNA damage response (DDR)-based treatments, allowing a reduction in dose of chemotherapy and radiation.
[0153] As shown in FIG. 1B, the efficiency of PRO140 binding to CCR5 positive cells was up to 98%.
[0159] A first subject enrolled in the study, subject 706-001, is a 42 year old female with Stage IV metastatic triple negative breast cancer. Subject has a history of left breast cancer with a right lung metastasis.
[0171] Following 16 weeks of leronlimab treatment of the first subject enrolled under the mTNBC study showed no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood. Furthermore, the patient had large reductions in CCR5 expression on cancer-associated cells after approximately 11 weeks of treatment with leronlimab. Additionally, the target lesion found on the right upper lobe of the lung nodule shows a greater than 20% decrease in size (as measured by tumor volume). This result was a remarkable improvement in disease outcome and demonstrates that leronlimab is a promising adjuvant therapy for the treatment of metastatic triple negative breast cancer.
[0172] A second subject with mTNBC was enrolled in the mTNBC study. Data collected from the second patient enrolled in the Company's mTNBC Phase 1b/2 trial showed no detectable levels of CTC after two weeks of treatment with the previously described treatment regimen of leronlimab in combination with carboplatin. This patient also showed a 70% reduction in EMT cells after just two weeks of treatment. Initial data from the second patient in the mTNBC trial indicated the CTC dropped to zero after two weeks of treatment with leronlimab. Additionally, the second patient had an initial CAML count of 45, and following at least two weeks of treatment the CAML count decreased to 30.
[0173] A third subject was enrolled in the mTNBC study. CTC+EMT counts were measured at initiation of treatment and two weeks following initiation of treatment with the previously described treatment regimen. The results indicate that the third patient's total CTC+EMT counts decreased by 75% during the first two weeks of treatment.
[0012] The present disclosure relates to the use of DNA damaging agents and leronlimab (PRO 140), or other anti-CCR5 agents, to treat or prevent cancer metastases and enhance the cell killing ability of the DNA damaging agents by selectively targeting the CCR5 receptor. The present disclosure relates to the use of DNA damaging agents and leronlimab (PRO 140), or other anti-CCR5 agents, to treat or prevent cancer metastases and reduce circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood following treatment, reduce CCR5 expression on cancer-associated cells after following treatment, decrease volume in tumor size following treatment. The present disclosure may be used to treat or prevent subjects with cancer and, particularly, subjects with metastatic CCR5+ cancer.
[0096] It has been found that leronlimab binds CCR5 in BCa cells, blocking breast cancer cellular invasion and tumor metastasis, 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 DNA damage response (DDR)-based treatments, allowing a reduction in dose of chemotherapy and radiation.
[0153] As shown in FIG. 1B, the efficiency of PRO140 binding to CCR5 positive cells was up to 98%.
[0159] A first subject enrolled in the study, subject 706-001, is a 42 year old female with Stage IV metastatic triple negative breast cancer. Subject has a history of left breast cancer with a right lung metastasis.
[0171] Following 16 weeks of leronlimab treatment of the first subject enrolled under the mTNBC study showed no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood. Furthermore, the patient had large reductions in CCR5 expression on cancer-associated cells after approximately 11 weeks of treatment with leronlimab. Additionally, the target lesion found on the right upper lobe of the lung nodule shows a greater than 20% decrease in size (as measured by tumor volume). This result was a remarkable improvement in disease outcome and demonstrates that leronlimab is a promising adjuvant therapy for the treatment of metastatic triple negative breast cancer.
[0172] A second subject with mTNBC was enrolled in the mTNBC study. Data collected from the second patient enrolled in the Company's mTNBC Phase 1b/2 trial showed no detectable levels of CTC after two weeks of treatment with the previously described treatment regimen of leronlimab in combination with carboplatin. This patient also showed a 70% reduction in EMT cells after just two weeks of treatment. Initial data from the second patient in the mTNBC trial indicated the CTC dropped to zero after two weeks of treatment with leronlimab. Additionally, the second patient had an initial CAML count of 45, and following at least two weeks of treatment the CAML count decreased to 30.
[0173] A third subject was enrolled in the mTNBC study. CTC+EMT counts were measured at initiation of treatment and two weeks following initiation of treatment with the previously described treatment regimen. The results indicate that the third patient's total CTC+EMT counts decreased by 75% during the first two weeks of treatment.
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