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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

(a) The transient decrease in PSA levels in two CRPC patients (60202 and 91760) who had minor responses. (b) A partial responder (60163) with the PSA levels declining by >50% within 6 months of completing therapy. (c) PostIT PSA levels in two nonresponding patients (FG00594 and FG00566) compared to their preIT baseline levels.
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fig2: (a) The transient decrease in PSA levels in two CRPC patients (60202 and 91760) who had minor responses. (b) A partial responder (60163) with the PSA levels declining by >50% within 6 months of completing therapy. (c) PostIT PSA levels in two nonresponding patients (FG00594 and FG00566) compared to their preIT baseline levels.

Mentions: There was a decrease in narcotic use in 2 of the 7 men possibly due to decreased bone pain. In addition to reduction of medication for bone pain associated with metastases, two CRPC patients with bulky disease infused with 40 (60202) and 80 (91760) billion Her2Bi-armed ATC, respectively, had minor responses observed as transient decreases in PSA levels (892 to 767 ng/mL and 1140 to 1046 ng/mL, resp.) that had short-term persistence after the last cell infusion (Figure 2(a)). A third CRPC patient (60163), who received 40 billion cells, had a partial response within 6 months of completing therapy with the patient's PSA levels decreasing by >50% (Figure 2(b)). Two patients showed an increase in their PSA levels after completion of 8 infusions of Her2Bi armed ATC compared to their preIT baseline levels (Figure 2(c)). Therapy was well tolerated and all patients received at least 80% of the planned dose. The doses administered, OS outcomes, and toxicities are included in Table 1. Our data show encouraging OS for a small cohort of men with HRPC.


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)

(a) The transient decrease in PSA levels in two CRPC patients (60202 and 91760) who had minor responses. (b) A partial responder (60163) with the PSA levels declining by >50% within 6 months of completing therapy. (c) PostIT PSA levels in two nonresponding patients (FG00594 and FG00566) compared to their preIT baseline levels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: (a) The transient decrease in PSA levels in two CRPC patients (60202 and 91760) who had minor responses. (b) A partial responder (60163) with the PSA levels declining by >50% within 6 months of completing therapy. (c) PostIT PSA levels in two nonresponding patients (FG00594 and FG00566) compared to their preIT baseline levels.
Mentions: There was a decrease in narcotic use in 2 of the 7 men possibly due to decreased bone pain. In addition to reduction of medication for bone pain associated with metastases, two CRPC patients with bulky disease infused with 40 (60202) and 80 (91760) billion Her2Bi-armed ATC, respectively, had minor responses observed as transient decreases in PSA levels (892 to 767 ng/mL and 1140 to 1046 ng/mL, resp.) that had short-term persistence after the last cell infusion (Figure 2(a)). A third CRPC patient (60163), who received 40 billion cells, had a partial response within 6 months of completing therapy with the patient's PSA levels decreasing by >50% (Figure 2(b)). Two patients showed an increase in their PSA levels after completion of 8 infusions of Her2Bi armed ATC compared to their preIT baseline levels (Figure 2(c)). Therapy was well tolerated and all patients received at least 80% of the planned dose. The doses administered, OS outcomes, and toxicities are included in Table 1. Our data show encouraging OS for a small cohort of men with HRPC.

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