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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

Number of IFN-γ producing cells when incubated overnight with prostate cancer cell line PC-3 in PBMC collected at baseline (preimmunotherapy [preIT]), during infusions (post inf#), and postimmunotherapy (1 week postimmunotherapy [1W postIT], 1 month postimmunotherapy [1 M postIT], and one year postimmunotherapy [1Y postIT]). (a) Increased number of IFN-γ producing cells during infusions and postIT time points in a partial responder (FG60163) when PBMC were incubated with prostate cancer specific PC-3 targets. (b) and (c) Enhanced IFN-γ responses in minor responders (FG60202 and FG91760).
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fig3: Number of IFN-γ producing cells when incubated overnight with prostate cancer cell line PC-3 in PBMC collected at baseline (preimmunotherapy [preIT]), during infusions (post inf#), and postimmunotherapy (1 week postimmunotherapy [1W postIT], 1 month postimmunotherapy [1 M postIT], and one year postimmunotherapy [1Y postIT]). (a) Increased number of IFN-γ producing cells during infusions and postIT time points in a partial responder (FG60163) when PBMC were incubated with prostate cancer specific PC-3 targets. (b) and (c) Enhanced IFN-γ responses in minor responders (FG60202 and FG91760).

Mentions: Fresh PBMC were stimulated with PC-3 cells to induce IFNγ EliSpots. Figures 3(a), 3(b), and 3(c) show the increases in IFNγ expressing cells after armed ATC infusions. There was a noticeable increase in the number of IFNγ EliSpots at postinfusion #5 compared to baseline (prior to armed ATC infusions [preIT]) in two patients (FG60163 and FG60202) and postinfusion #1 in third patient (FG91760). These data show that either memory helper T cells or cytotoxic T cells were induced by Her2Bi armed ATC infusions, preexist in the circulating peripheral blood lymphocytes, and respond immediately to direct stimulation with prostate tumor antigens on PC-3 targets.


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)

Number of IFN-γ producing cells when incubated overnight with prostate cancer cell line PC-3 in PBMC collected at baseline (preimmunotherapy [preIT]), during infusions (post inf#), and postimmunotherapy (1 week postimmunotherapy [1W postIT], 1 month postimmunotherapy [1 M postIT], and one year postimmunotherapy [1Y postIT]). (a) Increased number of IFN-γ producing cells during infusions and postIT time points in a partial responder (FG60163) when PBMC were incubated with prostate cancer specific PC-3 targets. (b) and (c) Enhanced IFN-γ responses in minor responders (FG60202 and FG91760).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Number of IFN-γ producing cells when incubated overnight with prostate cancer cell line PC-3 in PBMC collected at baseline (preimmunotherapy [preIT]), during infusions (post inf#), and postimmunotherapy (1 week postimmunotherapy [1W postIT], 1 month postimmunotherapy [1 M postIT], and one year postimmunotherapy [1Y postIT]). (a) Increased number of IFN-γ producing cells during infusions and postIT time points in a partial responder (FG60163) when PBMC were incubated with prostate cancer specific PC-3 targets. (b) and (c) Enhanced IFN-γ responses in minor responders (FG60202 and FG91760).
Mentions: Fresh PBMC were stimulated with PC-3 cells to induce IFNγ EliSpots. Figures 3(a), 3(b), and 3(c) show the increases in IFNγ expressing cells after armed ATC infusions. There was a noticeable increase in the number of IFNγ EliSpots at postinfusion #5 compared to baseline (prior to armed ATC infusions [preIT]) in two patients (FG60163 and FG60202) and postinfusion #1 in third patient (FG91760). These data show that either memory helper T cells or cytotoxic T cells were induced by Her2Bi armed ATC infusions, preexist in the circulating peripheral blood lymphocytes, and respond immediately to direct stimulation with prostate tumor antigens on PC-3 targets.

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