The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Luis H. Camacho - One of the best experts on this subject based on the ideXlab platform.
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Phase I clinical trials of Ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomez-navarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with Ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of Ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of Ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at >12 months (range: 13 - 42+) after initial treatment with Ticilimumab. This includes 5 pts with an OR who continue on Ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with Ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following Ticilimumab therapy. [Table: see text]
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Dose and schedule selection for the anti-CTLA4 monoclonal antibody Ticilimumab in patients (pts) with metastatic melanoma
Journal of Clinical Oncology, 2006Co-Authors: Jesus Gomez-navarro, C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, S. Eck, Luis H. CamachoAbstract:8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen se...
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Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb Ticilimumab
Journal of Clinical Oncology, 2006Co-Authors: Antoni Ribas, C. A. Bulanhagui, Viviana Bozon, Luis H. Camacho, Begoña Comin-anduix, Jason Jalil, Elizabeth Seja, Antonio Gualberto, James S. Economou, John A. GlaspyAbstract:8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of Ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received Ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical i...
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Ex vivo blood stimulation assay as a translational research tool in the development of the Ticilimumab (CP-675,206)
Journal of Clinical Oncology, 2006Co-Authors: Robert Millham, A. Ribas, Dmitri Pavlov, Luis H. Camacho, P. Canniff, D. Guyot, D. Hanson, Jesus Gomez-navarroAbstract:2542 Background: Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) is an activation-induced T lymphocyte negative costimulatory receptor which down-regulates cellular immune responses. CTLA4 blockade may break peripheral immunological tolerance, leading to an effective immune response to cancer. Tools for assessing the effects of such a blockade are limited, as CTLA4 is not constitutively expressed on circulating T cells, and because activated lymphocytes are difficult to access in vivo. Therefore, we have employed ex vivo blood stimulation assays to define pharmacodynamic properties of the anti-CTLA4 antibody, Ticilimumab. Methods: Ex vivo blood stimulation assays employed staphylococcal enterotoxin A (SEA) to stimulate isolated peripheral blood mononuclear cells (PBMC) or whole blood. Stimulation was monitored by production of interleukin 2 (IL-2). This assay was used preclinically to predict in vivo responses in animal models and in samples from cancer patients, as a batch release assay for productio...
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phase i clinical trials of Ticilimumab tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomeznavarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimum...
C. A. Bulanhagui - One of the best experts on this subject based on the ideXlab platform.
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Phase I clinical trials of Ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomez-navarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with Ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of Ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of Ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at >12 months (range: 13 - 42+) after initial treatment with Ticilimumab. This includes 5 pts with an OR who continue on Ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with Ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following Ticilimumab therapy. [Table: see text]
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Dose and schedule selection for the anti-CTLA4 monoclonal antibody Ticilimumab in patients (pts) with metastatic melanoma
Journal of Clinical Oncology, 2006Co-Authors: Jesus Gomez-navarro, C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, S. Eck, Luis H. CamachoAbstract:8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen se...
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Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb Ticilimumab
Journal of Clinical Oncology, 2006Co-Authors: Antoni Ribas, C. A. Bulanhagui, Viviana Bozon, Luis H. Camacho, Begoña Comin-anduix, Jason Jalil, Elizabeth Seja, Antonio Gualberto, James S. Economou, John A. GlaspyAbstract:8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of Ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received Ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical i...
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phase i clinical trials of Ticilimumab tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomeznavarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimum...
Viviana Bozon - One of the best experts on this subject based on the ideXlab platform.
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Phase I clinical trials of Ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomez-navarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with Ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of Ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of Ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at >12 months (range: 13 - 42+) after initial treatment with Ticilimumab. This includes 5 pts with an OR who continue on Ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with Ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following Ticilimumab therapy. [Table: see text]
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Dose and schedule selection for the anti-CTLA4 monoclonal antibody Ticilimumab in patients (pts) with metastatic melanoma
Journal of Clinical Oncology, 2006Co-Authors: Jesus Gomez-navarro, C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, S. Eck, Luis H. CamachoAbstract:8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen se...
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Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb Ticilimumab
Journal of Clinical Oncology, 2006Co-Authors: Antoni Ribas, C. A. Bulanhagui, Viviana Bozon, Luis H. Camacho, Begoña Comin-anduix, Jason Jalil, Elizabeth Seja, Antonio Gualberto, James S. Economou, John A. GlaspyAbstract:8033 Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of Ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received Ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical i...
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phase i clinical trials of Ticilimumab tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomeznavarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimum...
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Biologic and immunomodulatory events after CTLA-4 blockade with Ticilimumab in patients with advanced malignant melanoma†
Cancer, 2006Co-Authors: James M. Reuben, Viviana Bozon, Jesus Gomez-navarro, Bang Ning Lee, Charla A. Parker, Ingrid M. Hernandez, Carolina Gutierrez, Gabriel Lopez-berestein, Luis H. CamachoAbstract:BACKGROUND T-regulatory (TR) cells expressing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) maintain peripheral immune tolerance and negatively affect host immune responses against cancer. The immunobiologic effects of Ticilimumab, a human monoclonal antibody against CTLA-4, was administered to patients with metastatic melanoma who participated in a Phase I/II clinical trial. METHODS Thirty patients who received Ticilimumab at a dose of 10 mg/kg monthly (n = 20) or 15 mg/kg every 3 months (n = 10) were studied at study entry and at 14-day intervals thereafter to assess lymphocyte immunophenotypes, interleukin (IL)-2 and IL-10 production, and the expression of TR-related genes in peripheral blood mononuclear cells (PBMC) from a subset of patients was studied by real-time polymerase chain reaction. RESULTS Four of 12 patients with immune-related adverse events (IRAE) attained objective antitumor responses (ATR), whereas only 1 of 18 patients without IRAE attained ATR (χ2 = 4.0; P = .0455). Patients with ATR had significant reductions in TR cells and constitutive IL-10 production accompanied by a significant increase in IL-2 production by activated T cells. Although IRAE+/ATR+ patients demonstrated a positive correlation between CTLA-4 and glucocorticoid-induced tumor necrosis factor receptor (GITR) transcripts (Spearman rho = .522; P = .015), IRAE−/ATR− patients had a positive correlation between the transcripts of CTLA-4 and program death-1 (PD-1) receptor (Spearman rho = .891; P = .000). CONCLUSIONS Antitumor responses in patients with metastatic melanoma who were treated with Ticilimumab were found to be correlated with reductions in TR cells and constitutive secretion of IL-10, an increase in IL-2 production, and a positive correlation between transcripts of CTLA-4 and GITR. Conversely, a lack of ATR was found to be correlated with steady levels of TR cells and constitutive IL-10 secretion, and a positive correlation between the transcripts of CTLA-4 and PD-1. Cancer 2006. © 2006 American Cancer Society.
Dmitri Pavlov - One of the best experts on this subject based on the ideXlab platform.
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Phase I clinical trials of Ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomez-navarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with Ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of Ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of Ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at >12 months (range: 13 - 42+) after initial treatment with Ticilimumab. This includes 5 pts with an OR who continue on Ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with Ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following Ticilimumab therapy. [Table: see text]
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Dose and schedule selection for the anti-CTLA4 monoclonal antibody Ticilimumab in patients (pts) with metastatic melanoma
Journal of Clinical Oncology, 2006Co-Authors: Jesus Gomez-navarro, C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, S. Eck, Luis H. CamachoAbstract:8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen se...
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Ex vivo blood stimulation assay as a translational research tool in the development of the Ticilimumab (CP-675,206)
Journal of Clinical Oncology, 2006Co-Authors: Robert Millham, A. Ribas, Dmitri Pavlov, Luis H. Camacho, P. Canniff, D. Guyot, D. Hanson, Jesus Gomez-navarroAbstract:2542 Background: Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) is an activation-induced T lymphocyte negative costimulatory receptor which down-regulates cellular immune responses. CTLA4 blockade may break peripheral immunological tolerance, leading to an effective immune response to cancer. Tools for assessing the effects of such a blockade are limited, as CTLA4 is not constitutively expressed on circulating T cells, and because activated lymphocytes are difficult to access in vivo. Therefore, we have employed ex vivo blood stimulation assays to define pharmacodynamic properties of the anti-CTLA4 antibody, Ticilimumab. Methods: Ex vivo blood stimulation assays employed staphylococcal enterotoxin A (SEA) to stimulate isolated peripheral blood mononuclear cells (PBMC) or whole blood. Stimulation was monitored by production of interleukin 2 (IL-2). This assay was used preclinically to predict in vivo responses in animal models and in samples from cancer patients, as a batch release assay for productio...
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phase i clinical trials of Ticilimumab tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomeznavarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimum...
A. Ribas - One of the best experts on this subject based on the ideXlab platform.
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Phase I clinical trials of Ticilimumab: Tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomez-navarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with Ticilimumab, a fully human anti-CTLA4 mAb, have been reported previously. In both studies, objective responses (OR) were seen in some patients (pts) with melanoma. In addition, we observed highly favorable outcomes among several pts who did not experience objective responses. This may indicate a positive impact of Ticilimumab on melanoma in these pts, not well reflected by traditional response criteria. Long-term follow-up data on survival for pts enrolled in these Phase 1 studies is now reported. Methods: We studied the safety, pharmacokinetics, immunostimulatory activity, and clinical activity of Ticilimumab in 53 pts with solid malignancies. Ticilimumab was administered, as a single agent, at single dose levels ranging from 0.01 to 15 mg/kg and at multiple dose levels ranging from 3 to 15 mg/kg. The dosing regimens included either a single dose, multiple doses given q3 months, or multiple doses given q1 month. Results: The two studies included 43 pts with measurable melanoma. Ticilimumab proved safe and overall was well tolerated (Ribas et al. ProcASCO 2005, and JCO Dec2005). Of the 43 pts with measurable melanoma, 18 were alive at >12 months (range: 13 - 42+) after initial treatment with Ticilimumab. This includes 5 pts with an OR who continue on Ticilimumab, either on-study or as part of a single IND, and 13 pts without an objective response. Among the pts who did not experience an OR, 5 had surgical resection of metastatic lesions and remain relapse free, and 8 are alive with disease. Conclusions: In pts with melanoma treated with Ticilimumab, long-term survival has been achieved by all 5 pts who experienced an OR and in 13 pts who did not experience an OR. These findings suggest that lack of objective response is a poor predictor of long-term survival following Ticilimumab therapy. [Table: see text]
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Dose and schedule selection for the anti-CTLA4 monoclonal antibody Ticilimumab in patients (pts) with metastatic melanoma
Journal of Clinical Oncology, 2006Co-Authors: Jesus Gomez-navarro, C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, S. Eck, Luis H. CamachoAbstract:8032 Background: Ticilimumab therapy has demonstrated anti-tumor activity in pts with metastatic melanoma. Its indirect, immune-mediated antitumor effects pose unique challenges for dose/regimen se...
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Ex vivo blood stimulation assay as a translational research tool in the development of the Ticilimumab (CP-675,206)
Journal of Clinical Oncology, 2006Co-Authors: Robert Millham, A. Ribas, Dmitri Pavlov, Luis H. Camacho, P. Canniff, D. Guyot, D. Hanson, Jesus Gomez-navarroAbstract:2542 Background: Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) is an activation-induced T lymphocyte negative costimulatory receptor which down-regulates cellular immune responses. CTLA4 blockade may break peripheral immunological tolerance, leading to an effective immune response to cancer. Tools for assessing the effects of such a blockade are limited, as CTLA4 is not constitutively expressed on circulating T cells, and because activated lymphocytes are difficult to access in vivo. Therefore, we have employed ex vivo blood stimulation assays to define pharmacodynamic properties of the anti-CTLA4 antibody, Ticilimumab. Methods: Ex vivo blood stimulation assays employed staphylococcal enterotoxin A (SEA) to stimulate isolated peripheral blood mononuclear cells (PBMC) or whole blood. Stimulation was monitored by production of interleukin 2 (IL-2). This assay was used preclinically to predict in vivo responses in animal models and in samples from cancer patients, as a batch release assay for productio...
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phase i clinical trials of Ticilimumab tumor responses are sufficient but not necessary for prolonged survival
Journal of Clinical Oncology, 2006Co-Authors: C. A. Bulanhagui, A. Ribas, Dmitri Pavlov, Viviana Bozon, Amarnath Sharma, Jesus Gomeznavarro, Luis H. CamachoAbstract:8036 Background: Clinical studies examining anti-CTLA4 monoclonal antibodies (mAb) provide evidence of the biologic and clinical activity of this class of agents. Two Phase 1 studies with ticilimum...