Using Nanoparticles to Activate Immune Cells to Fight Tumors

Your method of fighting cancer of costimulation of B-cell receptor (BCR) and Toll-like receptor 7 (TLR7) with nanoparticles prior to injecting B cells is superior to injecting nanoparticles into the patient to stimulate T cells, BCR & TLR7, ie. Patent US20110104293 Example 21. The role of TLR7 in M2 macrophage polarization is intriguing.

Thank you Gail.

David, Thank you for your interest. But I want to clear up some areas of confusion. B cells express TRAF3 constitutively; they don't need exogenous stimuli. The nanoparticles are to enhance B cell uptake of antigen and adjuvant signals, which in turn makes them more effective APC. My lab performed a proof-of-concept of the B cell vaccine approach in an infectious disease mouse model; you can find the paper in The Journal of Immunology (2009). This paper would give you a clearer idea of our approach than I could provide in a quick paragraph. Using the approach for tumors is newer for us, and we need to do more work to be certain of the molecular mechanisms. We do know thta CD8 T cell activation is stimulated, but are not sure of the role of macrophages at this point. Best, GB

The nanoparticles must be needed to cause the B cells to express TRAF3. I am confident that this can be done with nanoparticles because Gail Bishop succeeded in doing it five years ago: "Differential TRAF3 utilization by a variant human CD40 receptor with enhanced signaling"

I think I understand your treatment now. Your B cells express TRAF3 which downregulates IL-10 to polarize macrophages to M1 type cells & undermine the tumors survival mechanism. Additional reference: "TNFR-Associated Factor-3 Is Associated With BAFF-R and Negatively Regulates BAFF-R-Mediated NF-B Activation and IL-10 Production"  . In summary, your treatment uses B cells expressing TRAF3 & newly polarized M1 cells to combat tumors. Thats a great idea. 

Since you are dealing with Melanoma, please keep this in mind: "Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation"  .Just in case your treatment of Melanoma falls short, you can might be able to work something out with this inventor: US20150080940 "Anti-tumor macrophage m1 morphology inducer" .You have an brilliant idea. No radiation. No chemotherapy. I am excited about the prospect of fighting cancer naturally with the immune system. I hope the FDA approves you all the way & doesnt limit your treatment availability & capabilities. The Burzynski Clinic was forced by the FDA to avoid tailor made treatments in replacing missing Histone Deacetylase Inhibitors resulting in questionable outcomes. Good luck.

Did I understand it right, when you say Bvac, does that mean that you are using "B cells" as antigen-presenting cells (APCs)? That you are applying Endogenous generated antigens from within the tumor cells (ie retroviruses, etc) & using the nanoparticles as an antigen catalyst to program the APCs that you removed before injecting them. I stand corrected from my previous entry. Keep up the good work.

Thank you, are you referring to: "Doxorubicin-Loaded Nanoparticles for the Induction of Anti-Tumor Immune Responses" Am I correct to say that they both involve the expression of Calreticulin?  ie UVB light induced retroviruses: "Pathophysiological Roles of Calreticulin in Autoimmune Disease" 

I'm sorry you got that incorrect impression, David. We are using Bvac as antigen presenting cells, NOT to make antibodies. This is quite a different goal. Regards, GB

You said that you wanted to create antibodies in Melanoma cells. You are reinventing the wheel. This can be done on the cheap, see "Transcriptional Activation of Endogenous Retroviral Sequences in Human Epidermal Keratinocytes by UVB Irradiation"

You said that you wanted to create antibodies in Melanoma cells. You are reinventing the wheel. This can be done on the cheap, see "Transcriptional Activation of Endogenous Retroviral Sequences in Human Epidermal Keratinocytes by UVB Irradiation"

Never give up! What you're doing is going to one day help so many people..Thank you for your dedication..

Good luck! I wish you much success in such important research!

I wish you and your team the very best of luck with this research!

Insurance for my later years.

Good Luck-Papa & Grammy

I'd love to learn more. Are there some papers or journal articles on your approach you can point me to? Thanks!

Hope your project gets funded and yields some useful results

Rooting for a breakthrough!

Glad to contribute

Good luck!

Good luck!