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Adjuvant-antigen requirements for active specific immunotherapy of microscopic metastases remaining after surgery
Abstract:
We studied the conditions required for eradication by immunization of occult lymph node metastases which remained after surgical removal of an intradermally transplanted cavian hepatoma. Guinea pigs that received no postsurgical treatment all died with progressively growing lymph node metastases. The growth of these metastases could be prevented in a significant proportion of the animals by postsurgical treatment with vaccines containing oil-in-water emulsions of Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG) cell walls admixed with live or irradiated tumor cells. Vaccines containing living tumor cells cured most of the guinea pigs but produced tumors at the vaccine sites in a few animals. Irradiated tumor cell vaccines were not tumorigenic but required more tumor cells for successful therapy. Therapy was dependent both on the dose of tumor cells and on that of BCG cell walls. Microgram doses of BCG cell walls were required for a therapeutic effect; milligram doses of BCG cell walls inhibited the therapeutic response. Animals rendered tumor free by postsurgical vaccine therapy rejected an intradermal challenge with living tumor cells.
Insights
Post-surgical immunization with Bacillus Calmette-Guérin (BCG) cell wall vaccines effectively eradicated occult lymph node metastases in guinea pigs. Optimal therapy required specific microgram doses of BCG cell walls and tumor cells, preventing tumor recurrence.
Area of Science:
- Immunology
- Oncology
- Veterinary Medicine
Background:
- Occult lymph node metastases pose a significant challenge after surgical tumor removal.
- Intradermal transplanted cavian hepatoma in guinea pigs serves as a model for studying metastasis.
- Postsurgical treatment is crucial for preventing the progression of residual cancer cells.
Purpose of the Study:
- To investigate the conditions necessary for eradicating occult lymph node metastases through immunization.
- To evaluate the efficacy of vaccines containing Mycobacterium bovis strain Bacillus Calmette-Guérin (BCG) cell walls and tumor cells.
- To determine the optimal dosage of BCG cell walls and tumor cells for successful immunotherapy.
Main Methods:
- Guinea pigs with surgically removed intradermal hepatoma were treated postsurgically with vaccines.
- Vaccines consisted of oil-in-water emulsions of BCG cell walls admixed with live or irradiated tumor cells.
- Therapeutic responses were assessed based on the prevention of lymph node metastases and animal survival.
Main Results:
- Postsurgical treatment with BCG cell wall vaccines significantly prevented the growth of lymph node metastases.
- Vaccines with live tumor cells achieved cures but carried a risk of local tumor formation.
- Irradiated tumor cell vaccines were safer but required higher cell doses; therapy efficacy depended on BCG and tumor cell dosage.
- Therapeutic effects were observed with microgram doses of BCG cell walls, while milligram doses were inhibitory.
- Animals cured by vaccine therapy demonstrated resistance to subsequent tumor cell challenges.
Conclusions:
- Immunization with specific BCG cell wall and tumor cell combinations can eradicate occult lymph node metastases.
- The dosage of BCG cell walls is critical, with microgram amounts being therapeutic and milligram amounts detrimental.
- Successful immunotherapy leads to long-term tumor-free survival and acquired immunity.