Journal of experimental therapeutics and oncology, 2006
Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playin... more Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playing a key role in angiogenesis. Angiogenesis is critical for tumor growth, and anti-angiogenic therapies have met clinical success. To validate the therapeutic potential of an anti-alpha5beta1 strategy, we generated volociximab (M200) a chimeric human IgG4 version of the alpha5beta1 function-blocking murine antibody IIA1; and F200, the Fab derivative. Volociximab, F200 and IIA1 showed similar activity by ELISA (EC50= 0.2nM), Biacore (Kd= 0.1-0.4nM) and inhibition of fibronectin binding (IC50= 2-3nM). The inhibitory potential of alpha5beta1 antibodies was compared to HuMV833, an anti-VEGF antibody. Both volociximab and HuMV833 inhibited HUVEC proliferation (IC50 of volociximab = 0.2-0.5nM; IC50 of HuMV833 = 45nM). However, IIA1, volociximab and F200 were also potent inhibitors of an in vitro model of angiogenesis (HUVEC tube formation assay), unlike HuMV833. Additionally, volociximab inhibi...
A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it i... more A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it is imperative to eliminate the cancer stem cells (CSCs) that drive tumor progression. The California Institute for Regenerative Medicine is supporting two novel approaches that target CSCs, one an antibody-mediated immunotherapy targeting CD47 and the other an antibody targeting ROR1. This article summarizes the evidence that CSCs are targeted and discusses the results of early clinical trials within the context of the CSC model.
Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell surface glycoprotein, ... more Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell surface glycoprotein, which is highly and uniformly expressed in multiple myeloma. Elotuzumab has demonstrated significant anti-tumor activity in pre-clinical mouse models of multiple myeloma (MM). The primary objective of this Phase I study is to evaluate the maximum tolerated dose (MTD) of elotuzumab in patients with relapsed/refractory MM. The study also evaluates the overall safety, pharmacokinetics (PK), biologic activity and clinical response to elotuzumab. Elotuzumab is administered every 2 weeks × 4 doses in six escalating dose cohorts ranging from 0.5 mg/kg to 20 mg/kg. An additional 4 doses may be administered if the patient demonstrates at least stable disease during the initial 4 doses of therapy. To date, a total of 23 patients, 52% male, with a median age of 64 years and a median of seven prior treatments, have been treated in the six cohorts. In the 2.5 mg/kg cohort, one out of six patients exp...
Introduction: We have recently shown that CS1 (CD2 subset 1, CRACC, SLAMF7), a cell surface glyco... more Introduction: We have recently shown that CS1 (CD2 subset 1, CRACC, SLAMF7), a cell surface glycoprotein of the CD2 family, is uniformly expressed on myeloma cells from multiple myeloma (MM) patients. Based on its high expression in MM and limited expression in normal cells, we propose CS1 as a novel and specific antibody target for the treatment of MM. Methods: A panel of monoclonal anti-CS1 antibodies (mAbs) was generated to identify a potential therapeutic candidate. MAb clones MuLuc63 and MuLuc90 were selected for testing in CS1 positive MM xenograft models in vivo in severe combined immunodeficient mice. HuLuc63, a humanized IgG1 version of MuLuc63, was generated as the potential therapeutic candidate for the treatment of MM. HuLuc63 and Fc-modified versions of HuLuc63 were tested for anti-tumor activity in mouse models vivo. In vitro antibody-dependent cellular cytotoxicity (ADCC) assays were performed to define the potential mechanism of action for HuLuc63. Results: Both MuLu...
The possible roles of the tyrosine kinase receptor EphA5 and its ligand Ephrin-A5 in axon guidanc... more The possible roles of the tyrosine kinase receptor EphA5 and its ligand Ephrin-A5 in axon guidance and axon fasciculation are reviewed.
Journal of experimental therapeutics and oncology, 2006
Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playin... more Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playing a key role in angiogenesis. Angiogenesis is critical for tumor growth, and anti-angiogenic therapies have met clinical success. To validate the therapeutic potential of an anti-alpha5beta1 strategy, we generated volociximab (M200) a chimeric human IgG4 version of the alpha5beta1 function-blocking murine antibody IIA1; and F200, the Fab derivative. Volociximab, F200 and IIA1 showed similar activity by ELISA (EC50= 0.2nM), Biacore (Kd= 0.1-0.4nM) and inhibition of fibronectin binding (IC50= 2-3nM). The inhibitory potential of alpha5beta1 antibodies was compared to HuMV833, an anti-VEGF antibody. Both volociximab and HuMV833 inhibited HUVEC proliferation (IC50 of volociximab = 0.2-0.5nM; IC50 of HuMV833 = 45nM). However, IIA1, volociximab and F200 were also potent inhibitors of an in vitro model of angiogenesis (HUVEC tube formation assay), unlike HuMV833. Additionally, volociximab inhibi...
A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it i... more A key implication of the cancer stem cell model is that for a cancer therapy to be curative, it is imperative to eliminate the cancer stem cells (CSCs) that drive tumor progression. The California Institute for Regenerative Medicine is supporting two novel approaches that target CSCs, one an antibody-mediated immunotherapy targeting CD47 and the other an antibody targeting ROR1. This article summarizes the evidence that CSCs are targeted and discusses the results of early clinical trials within the context of the CSC model.
Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell surface glycoprotein, ... more Elotuzumab is a humanized monoclonal antibody directed against CS1, a cell surface glycoprotein, which is highly and uniformly expressed in multiple myeloma. Elotuzumab has demonstrated significant anti-tumor activity in pre-clinical mouse models of multiple myeloma (MM). The primary objective of this Phase I study is to evaluate the maximum tolerated dose (MTD) of elotuzumab in patients with relapsed/refractory MM. The study also evaluates the overall safety, pharmacokinetics (PK), biologic activity and clinical response to elotuzumab. Elotuzumab is administered every 2 weeks × 4 doses in six escalating dose cohorts ranging from 0.5 mg/kg to 20 mg/kg. An additional 4 doses may be administered if the patient demonstrates at least stable disease during the initial 4 doses of therapy. To date, a total of 23 patients, 52% male, with a median age of 64 years and a median of seven prior treatments, have been treated in the six cohorts. In the 2.5 mg/kg cohort, one out of six patients exp...
Introduction: We have recently shown that CS1 (CD2 subset 1, CRACC, SLAMF7), a cell surface glyco... more Introduction: We have recently shown that CS1 (CD2 subset 1, CRACC, SLAMF7), a cell surface glycoprotein of the CD2 family, is uniformly expressed on myeloma cells from multiple myeloma (MM) patients. Based on its high expression in MM and limited expression in normal cells, we propose CS1 as a novel and specific antibody target for the treatment of MM. Methods: A panel of monoclonal anti-CS1 antibodies (mAbs) was generated to identify a potential therapeutic candidate. MAb clones MuLuc63 and MuLuc90 were selected for testing in CS1 positive MM xenograft models in vivo in severe combined immunodeficient mice. HuLuc63, a humanized IgG1 version of MuLuc63, was generated as the potential therapeutic candidate for the treatment of MM. HuLuc63 and Fc-modified versions of HuLuc63 were tested for anti-tumor activity in mouse models vivo. In vitro antibody-dependent cellular cytotoxicity (ADCC) assays were performed to define the potential mechanism of action for HuLuc63. Results: Both MuLu...
The possible roles of the tyrosine kinase receptor EphA5 and its ligand Ephrin-A5 in axon guidanc... more The possible roles of the tyrosine kinase receptor EphA5 and its ligand Ephrin-A5 in axon guidance and axon fasciculation are reviewed.
Uploads
Papers by Ingrid Caras