Dear Aliabbas,

The use of BCG to treat diseases:

Mycobacteria

Leprosy: BCG has a protective effect against leprosy in the range of 26 to 41% based on controlled trials. The protective effect is somewhat larger based on case control and cohort studies—about 60%.[18][19] However BCG vaccine is not used specifically to control leprosy.

Buruli ulcer: BCG may protect against or delay the onset of Buruli ulcer.[20]

Cancer immunotherapy

See also: Cancer immunotherapy, Cancer vaccine and Coley's toxins

Micrograph showing granulomatousinflammation of bladder neck tissue due to Bacillus Calmette-Guérin used to treat bladder cancer, H&E stain

A number of cancer vaccines use BCG as an adjuvant to provide an initial stimulation of the persons` immune systems.

BCG is used in the treatment of superficial forms of bladder cancer. Since the late 1970s, evidence has become available that instillation of BCG into the bladder is an effective form of immunotherapy in this disease.[21] While the mechanism is unclear, it appears a local immune reaction is mounted against the tumor. Immunotherapy with BCG prevents recurrence in up to 67% of cases of superficial bladder cancer.

Colorectal cancer[22]

Lung cancer[23]

Melanoma[24]

MPNST[25]

Equine sarcoid (in horses)

Type I diabetes[edit]

Diabetes, type 1: Clinical trials based on the work of Denise Faustman use BCG to induce production of TNF-α, which can kill the T-cells responsible for type 1 diabetes. In a Phase I, double-blind, placebo-controlled trial, two doses of the BCG vaccine were administered to three adults with long-term type 1 diabetes, resulting in elimination of the pancreas-harming cells, induction of regulatory T cells (Tregs) and a transient rise in C-peptide levels, suggestive of temporarily restored insulin production.[26]

[18] Setia MS, Steinmaus C, Ho CS, Rutherford GW. (2006). "The role of BCG in prevention of leprosy: a meta-analysis". Lancet Infect Dis 6 (3): 162–70. doi:10.1016/S1473-3099(06)70412-1. PMID 16500597.

[19] Merle, Corinne SC; Cunha, Sergio S; Rodrigues, Laura C (2010). "BCG vaccination and leprosy protection: Review of current evidence and status of BCG in leprosy control". Expert Review of Vaccines 9 (2): 209–22. doi:10.1586/ERV.09.161. PMID 20109030.

[20] Tanghe, A., J. Content, J. P. Van Vooren, F. Portaels, and K. Huygen (2001). "Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer". Infection and Immunity 69 (9): 5403–11. doi:10.1128/IAI.69.9.5403-5411.2001. PMC 98650. PMID 11500410.

[21] Lamm DL, Blumenstein BA, Crawford ED (1991). "A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guerin for transitional-cell carcinoma of the bladder". N Engl J Med 325 (2): 1205–9. doi:10.1056/NEJM199110243251703. PMC 1164610. PMID 1922207.

[22] Mosolits S, Nilsson B, Mellstedt H. (2005). "Towards therapeutic vaccines for colorectal carcinoma: a review of clinical trials". Expert Rev Vaccines 4 (3): 329–50. doi:10.1586/14760584.4.3.329. PMID 16026248.

[23] NAOTO MIYAZAWA; KEIICHI SUEMASU; TOSHIRO OGATA; TAKESHI YONEYAMA; TSUGUO NARUKE; RYOSUKE TSUCHIYA (1979). "BCG Immunotherapy as an Adjuvant to Surgery in Lung Cancer: A Randomized Prospective Clinical Trial". Jpn. J. Clin. Oncol. 9 (1): 19–26.

[24] Lu, CY; Lin, GC; Gu, JZ; Zhou, GY; Cao, Y (Sep 1994). "[A preliminary study of BCG adjuvant therapy in oral and maxillofacial malignant melanoma.].". Shanghai kou qiang yi xue = Shanghai journal of stomatology 3 (3): 144–5. PMID 16538310.

[25] Sari, Aysegul; Bal, Kaan; Tunakan, Mine; Ozturk, Cemil. "A case of a sporadic malignant peripheral nerve sheath tumor of the urinary bladder with concomitant in situ urothelial carcinoma treated by transuretheral resection". Indian Journal of Pathology and Microbiology 54 (1): 147. doi:10.4103/0377-4929.77376.

[26]  Faustman, DL; Wang L; Okubo Y; Burger D; Ban L; Man G; Zheng H; Schoenfeld D; Pompei R; Avruch J; Nathan D (Aug 2012). Doherty, T. Mark, ed. "Proof-of-Concept, Randomized, Controlled Clinical Trial of Bacillus-Calmette-Guerin for Treatment of Long-Term Type 1 Diabetes". PLoS ONE 7 (8): e41756. doi:10.1371/journal.pone.0041756. PMC 3414482. PMID 22905105.

Hoping this will be helpful,

Rafik

This was rapported

http://www.nature.com/nrmicro/journal/v4/n6/fig_tab/nrmicro1419_F2.html

for your question, combination of boosting with drug therapy , I don't know if it's worthy to do it, since expansion of T cells memory need a few days.

Aeras in Bethesda are trying to prime/boost the BCG immunization using BCG and recombinant protein expressing AG85 A and B, and rv3407.

By the way they are looking for a scientist in this field 

Thanks for your suggestions

We have investigated BCG in prime boost combinations as done by many investigators using either Ag or Ag epitopes to boost its immunogonecity..the question here is can it be used as therapeutic vaccine for pulmonary or tuberculous meningitis.. apart from other diseases and disorders.

Are there any papers related to such aspect. Kindly let me know.

Moreover it would be great if  the same can be discussed briefly by scientist expressing their views on the therapeutic aspect of BCG for TB

In Human this study was not evaluated. Even in some trials in 1920's BCG vaccination was done in positive Skin test, and uninfected subjects. and there was no difference in adults.

In guinea pig, BCG vaccination combined with drug therapy had better clinical and survival outcomes.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286658/#R3

Above two answers are very detailed and thanks for authors. For tuberculosis, BCG has already been used as booster with variable results.  I personally feel that BCG should be genetically altered to induce a better TH response if used as booster, and for this purpose the mechanisms of protective immunity should be investigated. We are working in that direction. The key questions are whether pre-existing immunity to primary BCG vaccination can be boosted and why BCG fails to induce long lasting central memory T cells as evident by its lack of protection against adult tuberculosis.

Thanks to all Authors for their detailed suggestions and answers. 

I'm working in same direction. Basically BCG has good protective effect against TBM in children, yet adults develop TBM disease. Considering good protective efficacy of BCG against TBM, it can be possibly tried with drug regimes, in animal models of TBM. We are working on that direction.. and are possibly open for collaboration.