IL-2: a review of current knowledge.
A limiting factor in the use of T-cell therapy for cancer has always been the ability to expand T-cells, whether derived from the peripheral blood, spleen or tumor. The availability of r-IL-2 has confirmed the feasibility of expanding T-cells and LAK cells for clinical trials after confirmation of their anti-tumor activity in murine models. While the most promising results using IL-2/LAK cells have been in patients with melanomas and renal cancer, anti-tumor effects have been seen in patients with a wide variety of cancers, even those with bulky tumors. This form of adoptive cellular biotherapy has confirmed that an expanded and activated cell population using the cancer research laboratory can provide a method by which clinicians can effectively treat advanced cancer. In tumor biopsies, the infiltrating lymphocytes have been recognised and are known to be cytolytically active for many years. Using IL-2 stimulation of growth and an ongoing antigen stimulation (tumor cells), we have maintained selective killing of tumor cells. Accessing cells and various factors in the medium which support and enhance T-cell growth and activation are being defined. The role of antigen stimulation is also basic to further progress with this technology. Tumor cell chunks and cultures, nude mouse xenografts, or purified antigen all represent potential sources of repeated antigen stimulation. Thus, the components are now available to develop a broad attack on advanced cancer using this laboratory-based technology of tumor-derived activated cell (TDAC) stimulation, expansion and therapy. These approaches and preliminary results point to the dramatic change in technology which has allowed the cancer research laboratory to be a substantial component in new clinical approaches to cancer treatment. Laboratory scientists have become a major component in the design and conduct of clinical trials using adoptive biotherapy. These techniques are laboratory based and it is only with close and effective communication between the laboratory scientists and the clinician that rapid and effective translation of these technologies to the patient will occur (20).
Oldham
R K
RK
Biotherapeutics, Inc., Cellular Immunology Section, Franklin, Tennessee 37064.
Maleckar
J R
JR
Yannelli
J R
JR
West
W H
WH
D000939:Epitopes / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000939:Epitopes; D007376:Interleukin-2