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The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting

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The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting. / Atanackovic, Djordje; Reinhard, Henrike; Meyer, Sabrina; Spöck, Stefanie; Grob, Tobias; Luetkens, Tim; Yousef, Sara; Cao, Yanran; Hildebrandt, York; Templin, Julia; Bartels, Katrin; Lajmi, Nesrine; Stoiber, Heribert; Kröger, Nicolaus-Martin; Atz, Judith; Seimetz, Diane; Izbicki, Jakob R; Bokemeyer, Carsten.

In: HUM VACC IMMUNOTHER, Vol. 9, No. 12, 01.12.2013, p. 2533-42.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Atanackovic, D, Reinhard, H, Meyer, S, Spöck, S, Grob, T, Luetkens, T, Yousef, S, Cao, Y, Hildebrandt, Y, Templin, J, Bartels, K, Lajmi, N, Stoiber, H, Kröger, N-M, Atz, J, Seimetz, D, Izbicki, JR & Bokemeyer, C 2013, 'The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting', HUM VACC IMMUNOTHER, vol. 9, no. 12, pp. 2533-42. https://doi.org/10.4161/hv.26065

APA

Atanackovic, D., Reinhard, H., Meyer, S., Spöck, S., Grob, T., Luetkens, T., Yousef, S., Cao, Y., Hildebrandt, Y., Templin, J., Bartels, K., Lajmi, N., Stoiber, H., Kröger, N-M., Atz, J., Seimetz, D., Izbicki, J. R., & Bokemeyer, C. (2013). The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting. HUM VACC IMMUNOTHER, 9(12), 2533-42. https://doi.org/10.4161/hv.26065

Vancouver

Atanackovic D, Reinhard H, Meyer S, Spöck S, Grob T, Luetkens T et al. The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting. HUM VACC IMMUNOTHER. 2013 Dec 1;9(12):2533-42. https://doi.org/10.4161/hv.26065

Bibtex

@article{98cd9b15852b4c0e9a3759eccaaed092,
title = "The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting",
abstract = "BACKGROUND: Patients with gastric cancer benefit from perioperative chemotherapy, however, treatment is toxic and many patients will relapse. The trifunctional antibody catumaxomab targets EpCAM on tumor cells, CD3 on T cells, and the Fcγ-receptor of antigen-presenting cells. While in Europe catumaxomab is approved for treating malignant ascites, it has not been investigated in the perioperative setting and its exact immunological mode of action is unclear.METHODS: In our study, gastric cancer patients received neoadjuvant platinum-based chemotherapy, one intraoperative application of catumaxomab, and 4 postoperative doses of intraperitoneal catumaxomab. Immunomonitoring was performed in 6 patients before surgery, after completion of catumaxomab treatment, and one month later.RESULTS: Intraperitoneal application of catumaxomab caused an increased expression of activation markers on the patients' T cells. This was accompanied by a transient decrease in numbers of CXCR3(+) effector T cells with a T-helper (Th)-1 phenotype in the peripheral blood. All patients evidenced pre-existing EpCAM-specific CD4(+) and/or CD8(+) T cells. While these cells transiently disappeared from the blood stream after intraperitoneal application of catumaxomab, we detected increased numbers of peripheral EpCAM-specific cells and a modified EpCAM-specific T-cell repertoire 4 weeks after completion of treatment. Finally, catumaxomab also amplified humoral immunity to tumor antigens other than EpCAM.CONCLUSIONS: Our findings suggest that catumaxomab exerts its clinical effects by (1) activating peripheral T cells, (2) redistributing effector T cells from the blood into peripheral tissues, (3) expanding and shaping of the pre-existing EpCAM-specific T-cell repertoire, and (4) spreading of anti-tumor immunity to different tumor antigens.",
author = "Djordje Atanackovic and Henrike Reinhard and Sabrina Meyer and Stefanie Sp{\"o}ck and Tobias Grob and Tim Luetkens and Sara Yousef and Yanran Cao and York Hildebrandt and Julia Templin and Katrin Bartels and Nesrine Lajmi and Heribert Stoiber and Nicolaus-Martin Kr{\"o}ger and Judith Atz and Diane Seimetz and Izbicki, {Jakob R} and Carsten Bokemeyer",
year = "2013",
month = dec,
day = "1",
doi = "10.4161/hv.26065",
language = "English",
volume = "9",
pages = "2533--42",
journal = "HUM VACC IMMUNOTHER",
issn = "2164-5515",
publisher = "LANDES BIOSCIENCE",
number = "12",

}

RIS

TY - JOUR

T1 - The trifunctional antibody catumaxomab amplifies and shapes tumor-specific immunity when applied to gastric cancer patients in the adjuvant setting

AU - Atanackovic, Djordje

AU - Reinhard, Henrike

AU - Meyer, Sabrina

AU - Spöck, Stefanie

AU - Grob, Tobias

AU - Luetkens, Tim

AU - Yousef, Sara

AU - Cao, Yanran

AU - Hildebrandt, York

AU - Templin, Julia

AU - Bartels, Katrin

AU - Lajmi, Nesrine

AU - Stoiber, Heribert

AU - Kröger, Nicolaus-Martin

AU - Atz, Judith

AU - Seimetz, Diane

AU - Izbicki, Jakob R

AU - Bokemeyer, Carsten

PY - 2013/12/1

Y1 - 2013/12/1

N2 - BACKGROUND: Patients with gastric cancer benefit from perioperative chemotherapy, however, treatment is toxic and many patients will relapse. The trifunctional antibody catumaxomab targets EpCAM on tumor cells, CD3 on T cells, and the Fcγ-receptor of antigen-presenting cells. While in Europe catumaxomab is approved for treating malignant ascites, it has not been investigated in the perioperative setting and its exact immunological mode of action is unclear.METHODS: In our study, gastric cancer patients received neoadjuvant platinum-based chemotherapy, one intraoperative application of catumaxomab, and 4 postoperative doses of intraperitoneal catumaxomab. Immunomonitoring was performed in 6 patients before surgery, after completion of catumaxomab treatment, and one month later.RESULTS: Intraperitoneal application of catumaxomab caused an increased expression of activation markers on the patients' T cells. This was accompanied by a transient decrease in numbers of CXCR3(+) effector T cells with a T-helper (Th)-1 phenotype in the peripheral blood. All patients evidenced pre-existing EpCAM-specific CD4(+) and/or CD8(+) T cells. While these cells transiently disappeared from the blood stream after intraperitoneal application of catumaxomab, we detected increased numbers of peripheral EpCAM-specific cells and a modified EpCAM-specific T-cell repertoire 4 weeks after completion of treatment. Finally, catumaxomab also amplified humoral immunity to tumor antigens other than EpCAM.CONCLUSIONS: Our findings suggest that catumaxomab exerts its clinical effects by (1) activating peripheral T cells, (2) redistributing effector T cells from the blood into peripheral tissues, (3) expanding and shaping of the pre-existing EpCAM-specific T-cell repertoire, and (4) spreading of anti-tumor immunity to different tumor antigens.

AB - BACKGROUND: Patients with gastric cancer benefit from perioperative chemotherapy, however, treatment is toxic and many patients will relapse. The trifunctional antibody catumaxomab targets EpCAM on tumor cells, CD3 on T cells, and the Fcγ-receptor of antigen-presenting cells. While in Europe catumaxomab is approved for treating malignant ascites, it has not been investigated in the perioperative setting and its exact immunological mode of action is unclear.METHODS: In our study, gastric cancer patients received neoadjuvant platinum-based chemotherapy, one intraoperative application of catumaxomab, and 4 postoperative doses of intraperitoneal catumaxomab. Immunomonitoring was performed in 6 patients before surgery, after completion of catumaxomab treatment, and one month later.RESULTS: Intraperitoneal application of catumaxomab caused an increased expression of activation markers on the patients' T cells. This was accompanied by a transient decrease in numbers of CXCR3(+) effector T cells with a T-helper (Th)-1 phenotype in the peripheral blood. All patients evidenced pre-existing EpCAM-specific CD4(+) and/or CD8(+) T cells. While these cells transiently disappeared from the blood stream after intraperitoneal application of catumaxomab, we detected increased numbers of peripheral EpCAM-specific cells and a modified EpCAM-specific T-cell repertoire 4 weeks after completion of treatment. Finally, catumaxomab also amplified humoral immunity to tumor antigens other than EpCAM.CONCLUSIONS: Our findings suggest that catumaxomab exerts its clinical effects by (1) activating peripheral T cells, (2) redistributing effector T cells from the blood into peripheral tissues, (3) expanding and shaping of the pre-existing EpCAM-specific T-cell repertoire, and (4) spreading of anti-tumor immunity to different tumor antigens.

U2 - 10.4161/hv.26065

DO - 10.4161/hv.26065

M3 - SCORING: Journal article

C2 - 23955093

VL - 9

SP - 2533

EP - 2542

JO - HUM VACC IMMUNOTHER

JF - HUM VACC IMMUNOTHER

SN - 2164-5515

IS - 12

ER -