The fibronectin attachment protein of bacillus Calmette-Guerin (BCG) mediates antitumor activity

Sinn, Haley W.; Elzey, Bennett D.; Jensen, Robert J.; Zhao, Xiuqin; Zhao, Weicheng; Ratliff, Timothy L.

doi:10.1007/s00262-007-0397-x

Cited by 27 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6), which appears to favor interactions with the urothelium313233. Finally, binding to fibronectin, described by several authors as being crucial to an efficient treatment343536, was increased when mycobacteria were in the emulsified form, indicating another advantageous character for efficacious attachment.…”

Section: Discussionmentioning

confidence: 93%

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Noguera-Ortega

Blanco-Cabra

Rabanal

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer.

show abstract

Section: Discussionmentioning

confidence: 93%

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Noguera-Ortega

Blanco-Cabra

Rabanal

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Although γ-irradiation is the least damaging treatment (Fig. 1) and metabolic activity is preserved 14 , the effect of irradiation could modify the physical properties of the mycobacterial surface as the structure of critical fibronectin-binding proteins 22 , affecting their recognition, internalization and trafficking, as well as the export of critical antigens needed to stimulate a proper immune response. Contrary to our results, other authors affirmed that heat-killed BCG or the cell wall skeleton of BCG enhanced the expression of dendritic cell activation markers 23,24 .…”

Section: Discussionmentioning

confidence: 99%

γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Subsequent in vivo studies, showed that intravesically-instilled, radiolabled recombinant FAP was able to bind bladder implanted tumors. Furthermore, intravesical recombinant FAP was capable of eliciting a T cell-dependent antitumor response in immunized mice indicating recombinant FAP, was internalized, processed and presented in context with MHC class I by bladder tumor cells 18 . Since FAP by itself was observed to mediate antitumor activity in FAP-immunized mice 18 , the possibility of using recombinant FAP protein alone as a lower-risk alternative to BCG for therapeutic purposes is currently being explored.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin attachment protein from bacillus Calmette‐Guerin as targeting agent for bladder tumor cells

Coon

Crist

Gonzalez-Bonet

et al. 2011

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The adjuvant therapy of choice for superficial bladder cancer is the intravesical instillation of live Mycobacterium bovis Bacillus Calmette-Guerin (BCG). In spite of the fact that this therapy is the most effective treatment for superficial bladder cancer, intravesical administration of BCG is associated with high local morbidity and the potential for systemic infection. Therefore, there is a need for the development of safer, less toxic approaches to fight this disease. Since fibronectin attachment protein (FAP) is a key element in BCG retention and targeting to cells, we hypothesize that this protein can be used as targeting agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here we evaluated the ability of bladder tumor cells to bind and endocytose FAP via fibronectin-integrin complexes. We found that microaggregation induced by an anti-FAP polyclonal antibody accelerated FAP uptake by T24 bladder tumor cells. FAP was determined to be internalized via a clathrin-independent, caveolae-dependent mechanism. Further, once within the endosomal compartment, FAP was targeted to the lysosomal compartment with negligible recycling to the plasma membrane. Importantly, we demonstrated that FAP microaggregation and internalization could also be triggered by multivalent Ni2+NTA-bearing liposomes. Overall, our studies validate the use of FAP as a targeting vector and provide the foundation for the design of more effective, less toxic bladder cancer therapeutics.

show abstract

The fibronectin attachment protein of bacillus Calmette-Guerin (BCG) mediates antitumor activity

Abstract: FAP is an effective antitumor agent that inhibits tumor growth at a level equivalent to that observed for BCG. This protein may thus provide an alternative to BCG for treatment of superficial bladder cancer.

Cited by 27 publications

References 37 publications

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria

Fibronectin attachment protein from bacillus Calmette‐Guerin as targeting agent for bladder tumor cells

Contact Info

Product

Resources

About