ASCO meeting and PD-1

As usual, there has been a flurry of news reports generated by the ASCO annual meeting in Chicago. One remarkable thing that happens is the VERY large number of wall street analysts that roam the convention center looking for some inside information that will enhance or kill an investment opportunity. This is a far cry from the way it used to be when only about 3000 folks attended this meeting in the 1970’s when I started going. Now it is something like a political convention complete with television feeds, huge convention spaces, and state-of-the art glitzy booths that are the size of a standard home building site. Ah, well….what else hasn’t changed in 40 years.

The “big news” I would say is the latest advance in the immune check-point therapies. It is nicely covered in this article from the New York Times today. Basically, the idea is that our immune system is carefully designed (intelligently or not) to avoid self attack. That is, when a virus or bacteria invades us, we need a quick response or we die. However, in many cases there is collateral damage. For example the inflammation can damage normal cells in the neighborhood. Think of the infected tooth and the swelling and pain surrounding the next tooth over. The self-limiting response requires some check-points that will prevent our response from doing too much damage and thus put out the fire before it spreads too far.

In the case of cancer, the response (very weak most of the time) is a cellular immune response (as opposed to antibodies of the type that neutralize bacteria and some viruses). The operators, called T-cells, have a huge variety of receptors, some of which allow the T-cells to attach to the tumor cells and cause their destruction. However, tumor cells also play in this game, and can display/release proteins that inactivate the T-cells. This is the body’s way of fending off an immune response that goes amok. “Don’t kill me, T-cell, I am part of the body you live in”. Manipulating these check-points is now possible with a variety of drugs, many being antibodies that inhibit either the ligand (signal) for Programmed Death (PD-L1) or its receptor (PD-1). You can read those links to get a more complete picture of the complexity.

To date, the main excitement has been in melanoma and kidney cancers, long known to be somewhat unique in their response to immune attack. The hope is that since we have evidence for some immune response that can be generated against prostate cancer with the approved “vaccine” sipuleucel-T, and the one in development, Prostvac, that these can be made more effective by adding the inhibitors of check-point blockers. Ipilimumab is already approved for melanoma and has been tried with some success in prostate cancer. Both “ipi” and others of the PD-1 blocker type are now in trials with the vaccines for prostate cancer. You can find those with searches at clinicaltrials.gov, but be aware that such trials are highly selective in eligibility and usually not available to patients with more advanced disease.