Tumor-infiltrating Lymphocytes In Patients Research Articles

Novel immunologic strategies in ovarian carcinoma

The purpose of our study was to develop new biologic systems for the treatment or diagnosis of patients with ovarian carcinoma through expansion of T-cell lines from the tumor-infiltrating lymphocytes of patients with ovarian carcinoma in low-dose recombinant interleukin-2 in sufficient numbers for treatment and human monoclonal antibodies that recognize cell-surface tumor-associated antigen determinants on ovarian carcinoma cells. Technologic advances in tumor immunology and new data presented in relation to ovarian carcinoma were used to develop T-cell lines for the treatment of advanced ovarian carcinoma patients. Logarithmic expansion of T-cell lines was performed in a hollow-fiber bioreactor, and a pilot clinical trial was initiated to treat ovarian carcinoma patients with intraperitoneal tumor-infiltrating lymphocytes plus low-dose recombinant interleukin-2. Human hybridomas were produced by fusion of regional lymph node B cells with a heteromyeloma cell line SPATZ 4. Two ovarian carcinoma patients have been treated with tumor-infiltrating lymphocytes expanded to 1 x 10 10 to 1 x 10 10 with manageable side effects and evidence of biologic activity. Human monoclonal antibodies have been developed that recognize tumor-associated antigen determinants. Recombinant interleukin-2-expanded tumor-infiltrating lymphocytes and human monoclonal antibodies recognize different molecular entities on tumor cells and act by different mechanisms. These approaches may be complementary to one another in future treatment strategies for ovarian carcinoma.

Comparison of recombinant-interleukin-2-activated peripheral blood and tumor-infiltrating lymphocytes of patients with epithelial ovarian carcinoma: cytotoxicity, growth kinetics and phenotype.

We have compared the growth and tumor-directed cytotoxic efficacy of recombinant-interleukin-2-(rIL-2)-activated peripheral blood (PBL) and tumor-infiltrating lymphocytes (TIL) from patients with epithelial ovarian carcinoma. These studies demonstrated that TIL and PBL displayed similar levels of cytotoxicity and a broad range of target cell killing, as exemplified by their reactivity against autologous and allogeneic ovarian tumors as well as against tumor cell lines. No specificity of autologous tumor cell killing was manifested by TIL. Even though TIL of some patients showed higher proliferative activity (especially at the later times in rIL-2 culture) this was not a general phenomenon. In fact, in one case TIL did not proliferate at all, and in the other case the PBL proliferated more actively. While the cultures were composed primarily of CD3+ lymphocytes, the major cytotoxic cells displayed the CD56+ and CD16+ phenotype. Addition of OKT3 mAb to rIL-2 cultures resulted in an increased proliferative index, but showed only a minor effect on the cytotoxic potential of cultured lymphocytes. The therapeutic potential of rIL-2-activated TIL and PBL is discussed.

Retrovirus Packaging Cells

Retroviral vectors promote the efficient transfer of genes into a variety of cell types from many animal species. An important contribution to their utility was the development of retrovirus packaging cells, which allow the production of retroviral vectors in the absence of replication-competent virus. Because of their ability to transfer genes efficiently into cells that are difficult to transfect by other methods, retroviral vectors are prime candidates for gene transfer into human somatic cells. Indeed, a retroviral vector recently has been used to mark tumor infiltrating lymphocytes in patients with melanoma to follow the persistence and distribution of these cells following infusion into patients. Hopefully these vectors will soon be used for the treatment of disease by transfer of functional genes, or gene therapy. Here I will review the available packaging cell lines and their properties with a focus on their ultimate application to human gene therapy.

Localization of tumor-infiltrating lymphocytes in patients with malignant liver tumors.

Localization of tumor-infiltrating lymphocytes in patients with malignant liver tumors.

Tumor-infiltrating lymphocytes in patients with renal-cell carcinoma.

Tumor-infiltrating lymphocytes in patients with renal-cell carcinoma.