This application postulates that the accessibility of tumor tissue would greatly improve if the permeability of tumor blood vessels could be increased. Inflammatory substances are known which cause the formation of gaps in endothelial cell layers and permit passage of soluble and particulate serum components into the extravascular space. It is proposed to guide such inflammatory substances specifically to the tumor site by attaching them to tumor- seeking antibodies. It is speculated that initially natural leakage will allow small quantities of the antibody conjugates to enter the tumor tissue and to initiate a micro-inflammation which would facilitate an increased influx of more inflammatory conjugates until a massive inflammation can be established. At that point, the endothelial blood vessel walls will become highly permeable and the tumor tissue susceptible for diagnostic and therapeutic measures.The initial studies will be performed in (C3HXBalb/c)F1 mice with syngeneic Meth-A fibrosarcoma transplant and monoclonal antibodies against the Ly6 marker which is prominently expressed in this tumor. The Ly6 antibody will be conjugated with inflammatory mediators such an TNF, LPS, and cell wall components isolated from gram positive pneumococci. With experience with this tumor system in hand, the study will expand to human melanoma transplants in athymic nu/nu mice and antibodies against melanoma associated antigens.
