Immunoregulation by Bacterial Organisms and Their Role in the Immunotherapy of Cancer

Interferon-? conjugation to human osteogenic sarcoma monoclonal antibody 791T/36

“…But for these effector cells to exert anti-turnout effects, they either have to be stimulated within tumours, or following peripheral activation, traffic to and localize within tumours. This requirement has been well established in numerous trials with bacterial vaccines or subcellular fractions, such as cell wall preparations where deposition of agents in tumours often provokes a marked anti-tumour response [3,4], In contrast, systemic treatment is ineffective, or at best, induces a weak anti-tumour response. This is illustrated by the use of liposomes containing muramyl dipeptide or muramyl tripeptide to activate alveolar macrophages, so causing significant destruction of murine B16 melanoma lung metastases [20].…”

“…The use of monoclonal antibodies as carriers for so-called 'biological response modifiers' has so far received little attention, but this approach may be potentially valuable in immunotherapy as a method of focussing host immune responses in tumours, particularly metastatic deposits. This requirement has been well documented in studies showing that bacterial agents such as BCG, as well as subcellular fractions, exert a more pronounced anti-tumour effect when administered so as to localize in turnout deposits [3,4,30]. The concept of targeting immunomodulating agents has been developed further through the use of liposome-encapsulated muramyl dipeptide for localization in, and activation of, lung macrophages in the immunotherapy of pulmonary metastases [16].…”

One Hundred Years of Cancer Immunotherapy: A Critical Appraisal

“…In some of the patients (7 out of 17 with malignant melanoma and 1 out of 7 patients with lung cancer) clinical improvement was observed [80]. The therapeutic effectiveness of BCG or C. parvum was discussed in another review [69]. It was concluded that 'bacterial stimulants exert their greatest antitumor effects only when they are administered by intralesional injection or systemically under conditions leading to their localization in tumour deposits'.…”

“…Some of the first clinical results with BCG as a sequel of experimental results were summarized in 1974 [79]. It was found that the mode of BCG application was important: BCG applied to a scarified area induced immunorestoration whereas BCG injected intravenously had no effect [69]. The effectiveness of a nonviable mycobacterial vaccine consisting of Mycobacterium smegmatis cell wall skeleton and trehalose dimycolate attached to oil droplets was investigated in 34 patients with metastatic malignant melanoma or pulmonary metastasis.…”

“…In another publication [68], it was stated that: 'Conditions for AI [active immunotherapy] may not be identical in man and mice, and we must avoid being exclusive when extrapolating conclusions from experiments on mice to clinical protocols'. It might be of interest to mention that already in 1979 it was stated that 'animal models for immunopharmacology may be more useful, because they are more sensitive and more selective than animal models for tumour immunotherapy' [69].…”