Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re‐targeted by a bi‐specific monoclonal antibody

We have reported a 27% overall anti‐tumor response using i.p. immunotherapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re‐targeted with bi‐specific monoclonal antibody OC/TR, combined with soluble OC/TR and low‐dose recombinant interleukin‐2 (IL‐2). This treatment...

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Veröffentlicht in:International journal of cancer 1997-10, Vol.73 (2), p.211-219
Hauptverfasser: Lamers, Cor H.J., Bolhuis, Reinder L.H., Warnaar, Sven O., Stoter, Gerrit, Gratama, Jan W.
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container_end_page 219
container_issue 2
container_start_page 211
container_title International journal of cancer
container_volume 73
creator Lamers, Cor H.J.
Bolhuis, Reinder L.H.
Warnaar, Sven O.
Stoter, Gerrit
Gratama, Jan W.
description We have reported a 27% overall anti‐tumor response using i.p. immunotherapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re‐targeted with bi‐specific monoclonal antibody OC/TR, combined with soluble OC/TR and low‐dose recombinant interleukin‐2 (IL‐2). This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4−, 8+, 16−, 56−. Their OC/TR‐re‐targeted cytolytic activity against Igrov‐1 ovarian‐carcinoma cells was approximately as high in responders as in non‐responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4−, 8+) and they were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov‐1 cells was low in direct assays, and only slightly increased after additional in vitro re‐targeting with OC/TR. Systemically, the i.p. immunotherapy resulted in a transient lymphopenia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentrations of free, functional OC/TR, and very weak coating of circulating T lymphocytes with OC/TR. These peripheral‐blood T lymphocytes did not exert OC/TR‐re‐targeted cytolytic activity. Thus, locoregional OC/TR‐re‐targeted cellular immunotherapy resulted in substantial local immunomodulation and anti‐tumor effects but virtually no systemic immunomodulation. Int. J. Cancer 73:211–219, 1997. © 1997 Wiley‐Liss, Inc.
doi_str_mv 10.1002/(SICI)1097-0215(19971009)73:2<211::AID-IJC9>3.0.CO;2-Z
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This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4−, 8+, 16−, 56−. Their OC/TR‐re‐targeted cytolytic activity against Igrov‐1 ovarian‐carcinoma cells was approximately as high in responders as in non‐responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4−, 8+) and they were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov‐1 cells was low in direct assays, and only slightly increased after additional in vitro re‐targeting with OC/TR. Systemically, the i.p. immunotherapy resulted in a transient lymphopenia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentrations of free, functional OC/TR, and very weak coating of circulating T lymphocytes with OC/TR. These peripheral‐blood T lymphocytes did not exert OC/TR‐re‐targeted cytolytic activity. Thus, locoregional OC/TR‐re‐targeted cellular immunotherapy resulted in substantial local immunomodulation and anti‐tumor effects but virtually no systemic immunomodulation. Int. J. 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This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4−, 8+, 16−, 56−. Their OC/TR‐re‐targeted cytolytic activity against Igrov‐1 ovarian‐carcinoma cells was approximately as high in responders as in non‐responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4−, 8+) and they were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov‐1 cells was low in direct assays, and only slightly increased after additional in vitro re‐targeting with OC/TR. 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source MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals
subjects Antibodies, Bispecific - therapeutic use
Antibodies, Monoclonal - therapeutic use
Ascitic Fluid - cytology
Biological and medical sciences
CD3 Complex - immunology
Cytotoxicity, Immunologic
Female
Flow Cytometry
Genital system. Mammary gland
Humans
Immunophenotyping
Immunotherapy
Infusions, Parenteral
Leukapheresis
Lymphocyte Activation - immunology
Lymphocyte Count
Medical sciences
Ovarian Neoplasms - immunology
Ovarian Neoplasms - therapy
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
title Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re‐targeted by a bi‐specific monoclonal antibody
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