Adjuvant chemotherapy and immunotherapy in high risk patients with melanoma.

Thirty-one patients with Stage II cutaneous melanoma received adjuvant chemotherapy or immunotherapy after radical excision of the primary and regional lymph nodes. Vaccinations with bacille Calmette Guérin produced minimal systemic reactions and was better tolerated by the patients than was chemotherapy. A higher survival rate and disease-free interval were noted in patients treated with bacille Calmette Guérin than those receving dimethyl Triazeno-imidazole carboximide. These results suggest that adjuvant chemotherapy with dimethyl Triazenoimidazole carboximide alone is not beneficial in the treatment of high risk patients with melanoma. In this study, adjuvant bacille Calmette Guérin therapy appears to be more advantageous than does chemotherapy.

Effectiveness of systemic BCG therapy in advanced melanoma.

The effect of systemic BCG therapy on advanced melanoma was studied in 42 patients with stage II and stage III disease. Evaluation of the immune response prior and during therapy revealed that patients who failed to convert a negative purified protein derivative (PPD) reaction and those having a low stimulation ratio of lymphocyte cultures had rapidly progressive disease and short survival. Neither tumor regression nor prolongation of survival could be appreciated in patients with stage III disease. Furthermore, aggravation of symptoms was observed in patients with visceral metastases. Fifty percent of the patients with stage II melanoma treated by operation and adjuvant immunotherapy had recurrent or metastatis disease within two years. No adverse effects were noted in patients with early disease who received adjuvant therapy. Two patients who had a full course of systemic BCG therapy developed severe reactions after intralesional injection of the vaccine. Further experience with various immunotherapeutic regimens and longer follow-up are necessary to evaluate its value in the early stages of melanoma.

The effect of pretreatment with allogeneic fetal cells on hamster melanoma.

Pretreatment with 7-day embryonic tissue mixed with incomplete adjuvant retarded the growth of melanoma transplants in the Syrian hamster. This effect was not apparent in animals treated with fetal tissue suspension, only or with fetal tissue and complete adjuvant. The inhibitory effect on tumor growth noted in animals challenged with tumor cell doses of 5 x 10(5) or 2.5 x 10(6) cells was abolished when the tumor dose was increased to 5 x 10(6). These results suggest that hamster melanoma and fetal tissue may share a common antigen.

RES blockade: effects on immunity and tolerance.

Reticuloendothelial cell blockade has been studied for decades in regards to physiological and immunological effects. "Overloading" of RE cells with inert colloidal particles, such as carbon or other particulate substances, has often been used to analyze the role of phagocytic activities in antibody formation, often with contrasting results. In the present studies the effects of colloidal carbon treatment of mice on immunologic responsiveness to sheep erythrocytes was investigated. Pre-treatment of mice with carbon shortly before either primary or secondary immunization with SRBCs markedly suppressed the expected antibody response, as shown by depressed numbers of hemolytic antibody plaque forming cells. Carbon treatment did not affect antibody forming cells per se as shown by lack of an effect on plaque forming cells when carbon was given after SRBCs, either in vivo or in vitro. Carbon injection before primary immunization prevented development of "immunologic memory," as shown by an altered secondary immune response. Mice given carbon and SRBC several weeks before secondary immunization with RBCs developed a primary type antibody response characterized by appearance of 19S antibody with little or no 7S hemolysins, characteristic of a secondary response. Furthermore, by appropriate treatment of mice with carbon and SRBC, immunologic unresponsiveness to SRBCs could also be induced, as evident by absence of both 19S and 7S antibody formation after subsequent challenge immunization with sheep erythrocytes. The mechanisms involved in RE "blockade" induced aberrations of normal immune responses may be related to effects on macrophages or soluble humoral factors, or both. It is unlikely that carbon treatment affects immunocytes directly. Further studies concerning the nature and mechanism of RE blockade on cellular and humoral components of the immune response mechanisms seem warranted and should provide more insight concerning the role of macrophages in antibody formation.