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Specificity of cell membrane antigens in prostatic cancer
Abstract:
Mice bearing a 3-methylcholanthrene-induced fibrosarcoma (MCAM-7) transplant in the right leg underwent surgical excision of the tumor and showed specific resistance to subsequent challenges with that identical tumor line. An in vivo response to tumor-specific antigens (MCAM-7 antigen) solubilized by hypertonic potassium chloride was measured by 24-hour footpad swelling response in mice immunized to the tumor from which the antigens were extracted. These observations suggested that the transplantable MCAM-7 fibrosarcoma could produce immunity toward the solubilized MCAM-7 tumor antigens and that this tumor immunity could be measured by footpad swelling response to injection of the solubilized antigens, an indication of cell-mediated immunity. The footpad swelling response was also minotored in relation to the extent of tumor growth. Mice received MCAM-7 tumor transplants by injection of 5 times 10-6 tumor cells and were tested for footpad swelling response at intervals following tumor transfer. A significant footpad response to injected MCAM-7 antigens was present 10 days following tumor transfer; at this time signs of tumor growth were only minimally detectable. The footpad swelling response to injected antigens disappeared by 28 days following initial tumor transfer; at this time the tumor diameters were in excess of 1.0 cm. Surgical removal of tumor at this point promptly restored footpad responses within 24 hours. Similar techniques have been applied to patients bearing adenocarcinoma of the prostate, where skin testing was substituted for the measurement of footpad swelling in animals. Seven patients with known prostatic carcinoma were given intradermal injections of soluble tumor antigens extracted from their own tumors. Three of the seven patients exhibited a cutaneous delayed type hypersensitivity response to the injected autologous tumor extracts. No positivereactions were observed in response to solubilized components of control tissues, including benign prostatic hyperplasia. The significance of the demonstrated concomitant immunity in these patients has not been resolved. However, these observations suggest that some patients bearing adenocarcinoma of the prostate can exhibit an immunologic response to specific antigens present in their own neoplasms.
Insights
Mice developed immunity to fibrosarcoma after tumor removal, measurable by footpad swelling. This immune response to tumor antigens was also observed in some prostate cancer patients, suggesting a potential for immunotherapy.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Surgical excision of tumors can induce specific anti-tumor immunity.
- Cell-mediated immunity plays a crucial role in anti-tumor responses.
- Assessing tumor-specific immune responses is vital for developing cancer immunotherapies.
Purpose of the Study:
- To investigate the development of tumor-specific immunity in mice after surgical removal of a fibrosarcoma.
- To evaluate the footpad swelling test as a measure of cell-mediated immunity to tumor antigens.
- To explore the presence of anti-tumor immune responses in patients with adenocarcinoma of the prostate.
Main Methods:
- Induction of fibrosarcoma (MCAM-7) in mice, followed by surgical tumor excision.
- Solubilization of tumor-specific antigens using hypertonic potassium chloride.
- Measurement of in vivo immune response via 24-hour footpad swelling test in mice.
- Intradermal injection of autologous tumor antigens in prostate cancer patients, with skin testing for hypersensitivity.
Main Results:
- Mice surgically treated for MCAM-7 fibrosarcoma developed specific resistance to tumor rechallenge.
- Footpad swelling response to MCAM-7 antigens indicated cell-mediated immunity, detectable as early as 10 days post-transplant.
- This immune response waned with tumor growth but was restored upon surgical tumor removal.
- Three out of seven prostate cancer patients showed delayed type hypersensitivity to their own tumor antigens.
Conclusions:
- Transplantable fibrosarcoma can induce measurable tumor immunity.
- The footpad swelling test is a viable method for assessing cell-mediated immunity to tumor antigens.
- Some patients with adenocarcinoma of the prostate exhibit an immune response to their own tumor-specific antigens, indicating potential for immunotherapy.