Saturday, November 15, 2014

Commentary - Why checkpoint inhibitors need help and a little push for SCIB1

Commentary by Richard Goodfellow, June 2014, Scancell

Despite all the advances in melanoma treatments in the past 4 years, we're still not quite there yet!  I thought this essay was interesting...though you must keep in mind that the author is the chief executive officer of the company that makes SCIB1.  However, Bent has always held that dendritic cells will prove essential in really understanding and treating melanoma.

Excerpts:  "Checkpoint inhibitors enable the host immune system to resume its ability to recognize, attack, and destroy cancer cells.  Ipilimumab was the first.  Drugs blocking PD-1 and its ligand PD-L1 are in advanced trials.  However, checkpoint inhibitors cannot work...if the patient fails to mount an adequate immune response or if the tumor evolves so that is it no longer recognized by the pre-existing immune response."

"[Anti-] PD-1 drugs are being combined with ipi, tyrosine kinase inhibitors (sunitinib and erlotinib); with anti-CD27 antibody varlilumab; and BRAFi [to try to answer the lack] though side effects are often an issue with these combos."

"Taking the brake off T cells with checkpoint inhibitors whilst simultaneously pressing the accelerator using active immunotherapies is a logical next step...  Vaccines can stimulate 'de novo' immune responses, but until recently, none of the vaccines...have been able to produce potent T cells with the power and specificity to recognize and kill tumor cells.  Peptides and MAGE vaccines failed to show any advantage.  A phase 3 study of a virus encoding GM-CSF has shown  some promising results, but the patient must have accessible tumors."

"We would argue that this advantage can be obtained by using the power of dendritic cells, the 'generals of the immune response army'.  Our first product, SCIB1, is a DNA plasmid encoding an antibody with four melanoma-specific T cell epitopes grafted into its structures.  We use eletroporation (the use of electrical fields to increase DNA drug delivery efficiency by up to 1000 fold compared to conventional injection) in conjunction with IM injection to deliver SCIB1 to patients.  This results in the direct uptake of DNA into cells and also enhances the immune response by targeting the expressed hybrid antibody to dendritic cells via the CD64 receptor."

"Data from a Phase 1/2 clinical trial of SCIB1 in patients with advanced melanoma has shown high immune response rates, evidence of prolonged survival and tumor destruction with a benign side effect profile.  Median survival time in patients with Stage III/IV disease is now 30 months since patients entered the study.  Patients with resected Stage IV disease are all still alive 19-41 months since tumor removal.  This compares favorably with published survival rates for patients with resected disease where 50% of Stage IV patients usually die within 21 months of surgery."

Hmmm...  I haven't seen any published research data for SCIB1 yet.  Most of the pr...IS pr...being put out by the company or other pharma investments firms.  But....the trial is real, though only in the UK at this's the link:

Link to clinical trial with SCIB1  

Would love for this to hold the key!  We'll see what happens! - c

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