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

نویسندگان

  • C H Lamers
  • R L Bolhuis
  • S O Warnaar
  • G Stoter
  • J W Gratama
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Production and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy

Background:  Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodi...

متن کامل

Systemic Targeted Alpha Radiotherapy for Cancer

Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET) of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and ch...

متن کامل

Monoclonal Antibody Production Against Vimentin by Whole Cell Immunization in a Mouse Model

Background: Pancreatic carcinoma is the fourth-leading cause of cancer death in the United States and due to its late presentation, only few patients would be candidates for the curative treatment of pancreactomy. Monoclonal antibodies have brought hope to targeted therapy.Objectives: To identify new biomarkers, a panel of monoclonal antibodies was genera...

متن کامل

FoxP3+ Regulatory T Cells in Peripheral Blood of Patients with Epithelial Ovarian Cancer

Background: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4 +CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. Objectives: To investigate the percentage of CD4 +CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women ...

متن کامل

Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites.

Tumor-associated lymphocytes (TAL) were isolated from the ascitic fluid of patients with adenocarcinoma of the ovary. These cells proliferated and expanded by 100-600-fold as either CD3+ CD4+ or CD3+ CD8+ cultures in the presence of moderate concentrations (50-200 cetus units/ml) of recombinant interleukin 2 and reached high numbers (5 x 10(8)-1 x 10(9)). After expansion of 16 TAL samples from ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • International journal of cancer

دوره 73 2  شماره 

صفحات  -

تاریخ انتشار 1997