A new area of cancer treatment is based on the concept of utilizing biological modifiers to modulate components of the immune system and hence employ the host's own tumor combating systems to destroy the cancer. The biological modifiers of particular interest for this role are the class of soluble cellular products termed lymphokines. The lymphokines, Inteleukin-2, (T cell growth factor), gamma interferon and beta interferon are potent regulators of the immune response as shown by their capacity to enhance cytotoxic T cell, natural killer cell and macrophage tumoricidal responses in vitro. Additionally, Interleukin-2 and inteferon are known to interact in enhancing cytotoxic responses in vitro. Consequently, we will evaluate the utility of purified preparations of each lymphokine and combinations of these lymphokines for in vivo treatment of two tumors in a mouse animal model system. The two tumors are fibrosarcoma and a T cell lymphoma. In this animal model system, we will assess the usefulness of lymphokine administration on the survival rates of mice injected with either the fibrosarcoma or the T cell lymphoma, and we will also measure in vitro cytotoxic responses of lymphoctyes/macrophages recovered from treated and control animals. In addition, we will use in vitro studies of lymphokine-modulated cytotoxic T cell, natural killer cell and macrophage tumoricidal activity both to assess the potential usefulness of the three lymphokines in cancer therapy and to gain insight into the basic mechanism of action of lymphokine-mediated tumor killing. Furthermore, we will compare two modes of delivery of the lymphokines (injected adjacent to the tumor site and implantation of osmotic minipumps) since both modes have potential clinical usefulness. The T cell lymphoma may be of particular value in demonstrating not only the potential usefulness but also the possible limitations of lymphokine therapy since a tumor of lymphoid origin may respond to lymphocyte products and to immunosurveillance differently than a tumor of non-lymphoid origin.
