What is the most exciting clinical trial going on right now? "A"

Science (especially medicine) often doesn't accept that something actually works until after a clinical trial is complete, but we often understand how the science works before the trial is even defined. What clinical trials going on right now do you think could have the most earthshaking results?

Using HIV to cure cancer.

The actual trials are http://clinicaltrials.gov/ct2/sh... and http://clinicaltrials.gov/ct2/sh..., a collaboration between UPenn and Novartis using genetically engineered T-cells to treat cancer (specifically CML and CLL, although ALL is also being tested).

A similar trial is also going on at Baylor University: http://clinicaltrials.gov/ct2/sh.... From a quick search on ClincialTrials.org, it seems like they have begun other trials throughout the US

Much has already been written about these clinical trial especially by the NYTimes. A good read for the layman. 

• A Breakthrough Against Leukemia Using Altered T-Cells
• Novartis and Penn Unite On Anticancer Approach
• Immune System, Loaded With Remade T-cells, Vanquishes Cancer

It's as crazy as it sounds, surprisingly, it is not a terrible idea. To paraphrase, T-cells that are harvested from a patient are genetically modified using a modified form of HIV which alters the T-cell to attack specific receptors that are expressed on certain cancers. I go deeper into the underlying science in:

• Is the new Penn-Novartis treatment a potential cure for all cancers?
• How is HIV used for cellular immunotheraphy?

This is particularly exciting to me since it represents a new way of treating disease similar to the advent of therapeutic antibodies and nanoparticles. Cellular immunotherapy represents a more promising advance over other "next-gen" therapeutics like RNAi, conventional gene-therapy, and stem-cells.

However, there are several limits and giant hurdles to seeing this as an approved therapy.

• Off target effects are usually lethal. Already one colon cancer patient has been killed due to an "on-target, off-organ" effect where the T-cells were successful in attacking the colon cancer but also attacked her lungs. Molecular Therapy - Safer CARS
• On target effects have resulted in Cytokine storm due to an acute immune system response. These fevers and chills make the first week of treatment extremely dangerous for the patient and the risk-benefit ratio compared to the current standard of care is unknown.
• The reasonable and scientific fear of using HIV as a viral vector. Not because of the use of HIV since that's a fairly "mild" condition compared to stage IV cancer but due to the fear of oncogene instability which stalled gene-therapy research. In layman's terms, there is a chance that curing cancer might accidentally give the patient another type of cancer.
• The lack of precedence of approving a patient specific therapy. While cellular immunotherapy has been approved via Provenge, the FDA has relatively little experience with approving a trial that require developing an entire manufacturing process for a single patient.
• A bizarre number of registered trials using a similar strategy at the Chinese PLA General Hospital. It would be interesting to see how well designed those trials are since a poor result in China could significantly impact the trial design in the US. A similar incident in France also stalled Gene therapy research.

Despite all of these very real concerns, these are the trials that I have been paying the most attention to since their results may make or break the biopharma industry.