Immunotherapy of cancer--experience with primary sarcoma in the rat.
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Biomedical subjects
Publications and source records attributed to P Alexander.
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The effects of both mechanical trauma and regeneration on the growth of intraportally injected tumor in the rat liver were investigated using two-thirds partial hepatectomy (PH). Tumor grew at the excision scar when PH was performed less than 2 days before tumor injection (34/34 animals). However, when the PH was performed 4-7 days before injection, tumor developed within the regenerating lobe, but not at the scar (50/51). Injecting the same cell dose into rats with intact livers caused few tumors to develop in 12/30 animals. Intraportally injected 51Cr-labelled tumor cells distributed uniformly in the liver irrespective of the time after PH. Patterns of tumor take seen at different times after PH were not due to selective trapping of the injected cells. Liver extracts showed that epidermal growth factor-like activity was unaltered by PH, while heparin-binding growth factor activity peaked at 2 days post-PH, before the incidence of tumor growth in the parenchyma increased. We observed two peaks of DNA synthesis at days 1 and 4 post-PH by pulse labeling with [125I]deoxyuridine and bromodeoxyuridine. Bromodeoxyuridine immunohistochemistry showed the first peak to be confined to hepatocytes. The second peak involved non-hepatocytes and coincided with the beginning of enhanced tumor take in the regenerating lobe.
Evidence has accumulated in the last 15 years that many experimentally-induced tumours in animals carry a tumour-specific transplantation-type antigen (TSTA) in their plasma membrane and that the tumour-bearing host responds to the TSTAs with the production of antibodies and cytotoxic mononuclear cells. In man the situation is not yet clear but there are indications that a similar situation may apply in many human malignancies. These findings have led to a resurgence in interest in the role of immunotherapy in the treatment of malignant disease, but as yet there is no clear evidence from properly controlled clinical trials that immunotherapy is the treatment of choice for any tumour. At present clinical immunotherapy constitutes a field for careful investigation but it cannot be considered a proven modality of treatment. At present its use must be confined to controlled studies in which benefit or possible harm can be determined. When giving immunotherapy it is necessary to monitor carefully the specific immune reaction of the host against the tumour. Further progress in immunotherapy requires a better understanding of why tumour cells succeed in vivo to escape destruction by the immune responses of the host. This review summarizes the current state of knowledge concerning the nature of TSTAs, the effect of the immune response to TSTAs on metastatic spread and the mechanisms of escape with special reference to the role which circulating soluble TSTA plays in 'neutralizing' the action of cytotoxic cells and antibodies. It is stressed that there is no support for the hypothesis of a 'blocking antibody'. Finally the different types of immunotherapy which have been developed in animal systems are described and possible clinical applications are discussed.
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