Immunotherapy and chemoimmunotherapy of malignant disease with BCG and nonviable mycobacterial fractions

Abstract

The administration of Bacillus Calmette‐Guérin (BCG) has been associated with restoration of general immunocompetence, augmentation of specific tumor immunity, activation of local and regional host defense mechanisms, and stimulation of the reticuloendothelial system. There is evidence that antigens from a variety of unrelated tumors are shared with, or are similar to, antigens in BCG. However, it is uncertain whether this cross‐reactivity is the basis for the antitumor activity of BCG. Numerous studies emphasize the importance of regional effects of immunotherapy. They suggest a two‐step mechanism for antitumor activity that involves recognition of BCG by host defense mechanisms, followed by activation and mobilization of macrophages by specifically produced lymphokines. The several nonviable derivatives of BCG have activity comparable to BCG without many of the problems associated with viable BCG. An optimal, completely standardized BCG preparation has not yet been produced. Clinical studies on the immunotherapeutic effects of BCG and its derivatives in cancer patients indicate that in cutaneous malignant melanoma, intralesional injection of BCG causes complete regression of tumor in 65–90% of instances, with long‐term remission in patients with purely cutaneous metastatic disease. In patients with disseminated malignant melanoma, studies show prolongation of remission duration and overall survival in patients undergoing chemoimmunotherapy (with BCG + imidazole carboxamide) over those receiving chemotherapy alone. In acute lymphoblastic leukemia, one study has found a greater than 90% probability of survival in patients with the microlymphoblastic type undergoing immunotherapy after 5 years, yet other studies fail to show any therapeutic advantage. In most studies in acute myeloblastic leukemia, immunochemotherapy has given both qualitative and quantitative improvements in remission duration and particularly survival. Increased survival, particularly in stage I patients, has been reported in a trial of adjuvant BCG immunotherapy in lung cancer. Other studies on carcinoma of the colon, breast, and the head and neck, soft tissue sarcomas, and genitourinary cancers, utilizing various combinations of BCG and its derivatives, and chemotherapy, surgery, or radiation therapy indicate enhanced remission duration and survival. However, more research is needed to determine the optimum therapy combination in each case, to make refinements in dose, route, and schedule of administration, to improve product characteristics, and to overcome the complications of BCG immunotherapy.

Effects of Intravenous and Intracutaneous Bacillus Calmette-Guérin Application on the Drug-Metabolizing System of the Liver

“…lymphomas, carcinomas of the breast and lung, sarcomas, leukemia, etc. [8], Despite the ever-increasing experiences about the clinical efficiency the benefit of BCG therapy either alone or in combination with chemotherapeutical agents like dimethyl-triazeno-imidazole-carboxamide (DTIC, Dacarbazine) is not yet unequivocally established [5,8], DTIC, like most of the chemotherapeutic substances, is metabolized by liver microsomal enzymes. It undergoes N-demethylation resulting in formal dehyde and aminoimidazole-carboxamide (AIC) formation [9], The dealkylating enzymes in the liver belong to the microsomal mixed-function oxy genase system.…”