Friday, April 24, 2015

Immunotherapy drug,Dana Farber, Stephan Hodi..


F. Stephen Hodi, MD. Credit: Sam Ogden, Dana-Farber
A promising experimental immunotherapy drug works best in patients whose immune defenses initially rally to attack the cancer but then are stymied by a molecular brake that shuts down the response, according to a new study led by researchers at Dana-Farber Cancer Institute and the Yale University School of Medicine.
The antibody drug, known as MPDL3280A, inhibits the brake protein, PD-L1, reviving the response by immune killer T cells, which target and destroy the . In recent clinical trials, the PD-L1 checkpoint blocker caused impressive shrinkage of kidney, melanoma, and lung tumors. But, as with other immunotherapy drugs, many  saw no benefit.  Researchers report in the November 27 edition of Nature that the antibody was most effective when the patients' immune cells surrounding tumors expressed PD-L1 - a sign that a pre-existing had been shut down by PD-L1. There was less tumor shrinkage in patients who never developed an immune response to the  - and, as a result, had less PD-L1 in the cancer and surrounding tissues.  "I think this is a launching point to use these findings as a predictive biomarker," said F. Stephen Hodi, MD, of Dana-Farber, senior author of the report. Hodi directs the Center for Immuno-Oncology and the Melanoma Treatment Center at Dana-Farber. First author is Roy Herbst, MD, PhD, chief of Medical Oncology at the Yale Comprehensive Cancer Center.  The scientists studied tumor tissue samples from 175 patients treated in clinical trials with MPDL3280A for advanced non-small cell lung cancer, melanoma, kidney cancer, and other cancers. On average, 18 percent of the patients had complete or partial shrinkage of their tumors, with higher or lower rates in different cancer types. Overall, the treatment was well-tolerated, with few severe side-effects, the report said.  An antibody stain that marked the presence of PD-L1 was applied to tumor samples that had been removed from patients prior to treatment. The stain revealed PD-L1 not only in the cancer cells, but also tumor-infiltrating immune cells (ICs). These are T cells and other cells of the immune response that had invaded the tumor in an attempt to destroy them.  The study found greater responses to the antibody drug in patients whose  and ICs were high in PD-L1. The scientists also looked at PD-L1 expression in samples taken from tumors while the patients were in treatment. They found that tumors that had shrunk as cells died showed increases in PD-L1 in the cancer and infiltrating immune cells.  From these findings, the researchers concluded that for the MPDL3280A antibody to be effective, the patient must have mounted an immune response that was beaten back by PD-L1. This creates a target for the PD-L1-blocking antibody, which removes the brakes on the response and allows the immune cells to attack the tumor.  The scientists called for further studies to define predictors of the response to PD-L1 blockers. "Understanding the profile of non-responders will likely provide even more valuable information," they said, "possibly revealing the diversity of mechanisms controlling anti-tumor immunity." 
  • Scientists analyzed tissue samples from patients who had - and had not - responded to a promising new immunotherapy drug
  • They found that patients did best whose cancers had expression of a protein, PD-L1, in  surrounding the tumor cells, to shut down an immune system attack against the cancer
  • The study could help identify patients most likely to respond to the new drug, which blocks PD-L1
More information: Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients, Nature, 515, 563–567 (27 November 2014) DOI: 10.1038/nature14011
Provided by Dana-Farber Cancer Institute

Sunday, April 19, 2015

Carly Fiorina in New Hampshire speech was fantastic

Luckily,  for me I awoke this early morning to see and hear on TV the speakers in New Hamshire this past week.  

I enjoyed Rand Paul speaking and of his hopes to make our country better and how he is trying even now in the Senate.

 Then Carly Fiorina came on and I  was amazed at her brilliance!  I should have realized , but  like many we don't often think about and or realize the  requirements one must have , to be in  the position of a leader of an international giant company.

  What a breath of fresh air to see this woman display her ability to think and lead. Each statement and answer was terrific and flowed from a high intelligence .

Carly brought home the value of her experience as a business woman  leading one of  the biggest companies in the world ,who has had experience with leaders all over the world .  Her response to questions was excellent especially the last question when asked to compare herself to other leading candidates .  Carly approached that question as a leader by answering " my experience is different",etc.  (I don't intend to simplify, the point is , it was the right answer without hurting anyone, simple and smart)

 She is breath taking in her brilliance!  It is difficult to summarize here .  If you have the chance to hear her speak , it is well worth  it.