Evaluation of the worth ofCorynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: Eight-year results from the national surgical adjuvant breast and bowel project B-10

Abstract

During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacteriurn parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease-free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow-up fail to indicate that treatment with CP used in conjunction with 1-phenylalanine mustard (L-PAM) plus 5-fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer. Cancer 66:220-227.1990.

Induction of CD4+ and CD8+ anti‐tumor effector T cell responses by bacteria mediated tumor therapy

“…Typhimurium) could demonstrate a safe administration of this therapeutic to human patients. However, tumor colonization and anti‐tumor effect was very limited in this studies most likely due to the strong attenuation of the applied strain . Therefore, developing a strain with an ideal attenuation level is one of the major goals to generate an applicable anti‐tumor bacterium.…”

“…However, tumor colonization and anti-tumor effect was very limited in this studies most likely due to the strong attenuation of the applied strain. 7,8 Therefore, developing a strain with an ideal attenuation level is one of the major goals to generate an applicable anti-tumor bacterium. The auxotrophic S. Typhimurium A1-R strain (leu/arg-dependent) is one such example of a strain that has been shown to be very effective against human tumors in T cell deficient mouse models.…”

Treatment of Leishmania (Leishmania) Amazonensis-Infected Mice with a Combination of a Palladacycle Complex and Heat-Killed Propionibacterium acnes Triggers Protective Cellular Immune Responses

“…The adjuvant effect of P. acnes , in the past classified as Corynebacterium parvum , was described due its capability to enhance tumoricidal and phagocytic macrophage function demonstrated in clinical and experimental models (Halpern et al, 1966; Fisher et al, 1990; Salomaa et al, 1995), besides its effects on infection resistance and antibody response (Warr and James, 1975; Brener and Cardoso, 1976). The mechanisms by which P. acnes modulates immune response such as increase of proinflammatory cytokine synthesis and modulation of Th2 to Th1 responses were demonstrated in experimental models of tumor and allergy among others (Matsui et al, 1997; Braga et al, 2003; Ananias et al, 2007; Squaiella-Baptistão et al, 2015).…”

Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli Nissle 1917 in live mice

“…Recently, obligate anaerobic bacteria such as Bifidobacterium (Kimura et al, 1980;Yazawa et al, 2000;Yi et al, 2005) Clostridia species (Parker et al, 1947;Malmgren and Flanigan, 1955;Gericke and Engelbart, 1964;Moese and Moese, 1964;Thiele et al, 1964;Lemmon et al, 1997;Dang et al, 2001;Agrawal et al, 2004) and Corynebacterium parvum (Fisher et al, 1990) as well as facultative anaerobes such as Salmonella (Salmonella typhimurium (Pawelek et al, 1997(Pawelek et al, , 2003Low et al, 1999;Zhao et al, 2005Zhao et al, , 2006, Salmonella choleraesuis (Lee et al, 2004(Lee et al, , 2005a), Bordetella pertussis (Pawelek, 2005) were used to achieve tumor therapy in mice. Tumor colonization also was observed after intravenous (i.v.)…”