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Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients.

Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG - Prostate Cancer (2015)

Bottom Line: Methods.There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Medicine, Wayne State University, Detroit, MI 48201, USA.

ABSTRACT
Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 10(9) aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.

No MeSH data available.


Related in: MedlinePlus

The treatment schema. Her2Bi armed ATC (aATC) were administered twice weekly for four consecutive weeks. All patients received subcutaneous IL-2 (300,000 IU/m2/day) and GM-CSF (250 μg/m2/twice weekly), beginning 3 days before the first aATC infusion and ending 1 week after the last aATC infusion. Immune testing was performed at indicated time points.
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fig1: The treatment schema. Her2Bi armed ATC (aATC) were administered twice weekly for four consecutive weeks. All patients received subcutaneous IL-2 (300,000 IU/m2/day) and GM-CSF (250 μg/m2/twice weekly), beginning 3 days before the first aATC infusion and ending 1 week after the last aATC infusion. Immune testing was performed at indicated time points.

Mentions: T cells were infused only after standard operating procedures for identifying the cryopreserved product and the patient at the bedside. The infusion rate was calculated based on an infusing rate of no more than 5 EU of endotoxin/kg/hour. Armed ATC were given over 5–15 mins with monitoring of vital signs before and every 15 mins up to 1 hr after infusion. All vital signs and side effects were recorded on the patient's chart using the NCI immunotherapy toxicity table. Patients were observed up to 6 hours after their infusions. The dose levels for each infusion were 2.5, 5, 10, and 20 billion. Each patient would receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encountered toxicities related to armed ATC, modifications of the dose or holding the administration was required. The patients also received subcutaneous injections of interleukin-2 [IL-2] (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250 μg/m2 twice per week) was administered starting 3 days before the first armed ATC infusion and ending 7 days after the last dose of armed ATC (Figure 1).


Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients.

Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG - Prostate Cancer (2015)

The treatment schema. Her2Bi armed ATC (aATC) were administered twice weekly for four consecutive weeks. All patients received subcutaneous IL-2 (300,000 IU/m2/day) and GM-CSF (250 μg/m2/twice weekly), beginning 3 days before the first aATC infusion and ending 1 week after the last aATC infusion. Immune testing was performed at indicated time points.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352947&req=5

fig1: The treatment schema. Her2Bi armed ATC (aATC) were administered twice weekly for four consecutive weeks. All patients received subcutaneous IL-2 (300,000 IU/m2/day) and GM-CSF (250 μg/m2/twice weekly), beginning 3 days before the first aATC infusion and ending 1 week after the last aATC infusion. Immune testing was performed at indicated time points.
Mentions: T cells were infused only after standard operating procedures for identifying the cryopreserved product and the patient at the bedside. The infusion rate was calculated based on an infusing rate of no more than 5 EU of endotoxin/kg/hour. Armed ATC were given over 5–15 mins with monitoring of vital signs before and every 15 mins up to 1 hr after infusion. All vital signs and side effects were recorded on the patient's chart using the NCI immunotherapy toxicity table. Patients were observed up to 6 hours after their infusions. The dose levels for each infusion were 2.5, 5, 10, and 20 billion. Each patient would receive a total of 8 doses of armed ATC given twice weekly for 4 weeks. If the patients encountered toxicities related to armed ATC, modifications of the dose or holding the administration was required. The patients also received subcutaneous injections of interleukin-2 [IL-2] (3.0 × 105 IU/m2/day) starting 3 days before the 1st armed ATC infusion and ending 7 days after the last armed ATC infusion. GM-CSF (250 μg/m2 twice per week) was administered starting 3 days before the first armed ATC infusion and ending 7 days after the last dose of armed ATC (Figure 1).

Bottom Line: Methods.There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores.Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA ; Department of Medicine, Wayne State University, Detroit, MI 48201, USA.

ABSTRACT
Background. New nontoxic targeted approaches are needed for patients with castrate resistant prostate cancer (CRPC). Our preclinical studies show that activated T cells (ATC) armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi) kill prostate cancer cells lines, induce a Th1 cytokine pattern upon engagement of tumor cells, prevent the development of prostate tumors, and retard tumor growth in immunodeficient mice. These studies provided strong rationale for our phase I dose-escalation pilot study to test ATC armed with Her2Bi (aATC) for safety in men with CRPC. Methods. Seven of 8 men with CRPC were evaluable after receiving two infusions per week for 4 weeks. The men received 2.5, 5 or 10 × 10(9) aATC per infusion with low dose interleukin-2 and granulocyte-macrophage colony stimulating factor. Results. There were no dose limiting toxicities, and there was 1 partial responder and 3 of 7 patients had significant decreases in their PSA levels and pain scores. Immune evaluations of peripheral blood mononuclear cells in 2 patients before and after immunotherapy showed increases in IFN-γ EliSpot responses and Th1 serum cytokines. Conclusions. These results provide a strong rationale for developing phase II trials to determine whether aATC are effective for treating CRPC.

No MeSH data available.


Related in: MedlinePlus