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ASCO: Immune Therapy
"...Herbst reported findings for 171 patients, 140 of whom could be evaluated for response. The study population included patients with lung cancer, kidney cancer, melanoma, colon cancer, stomach cancer, and head and neck cancer, and the patients had received a median of five prior therapies. .....
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
- A fifth of heavily pretreated patients with advanced cancers responded to a monoclonal antibody (MPDL3280A) that blocks a tumor's ability to hide from the immune system.
- Note that in another study, concurrent treatment with ipilimumab (Yervoy) and the PD-1 targeted drug nivolumab led to substantial tumor shrinkage in roughly half of patients with difficult to treat, advanced melanoma.
The American Association for Cancer Research (AACR) meeting held April 6 – 10 in Washington DC, provided a scientific perspective on oncologic developments. As opposed to the more clinical American Society of Clinical Oncology (ASCO), basic scientists attend this meeting, a large percentage of who are PhDs. The conference affords these investigators the opportunity to discuss their basic research and to present methodology workshops. The meeting also provides an early overview of the general direction that cancer research will be taking over the coming years, while ASCO reports what we’ve recently done, AACR reports what we will be doing.
ReplyDeleteIn his The Future of Cancer Research, Dr. Robert A. Nagourney described several overarching themes at this year’s meeting, the most prominent of these being the remarkable strides in immunologic therapy. Numerous investigators reported novel developments in the field. Where the immune system used to present as an insurmountable barrier of complexity, today we have dissected specific response elements and immune suppressive pathways that offer unique opportunities for therapy. Immunologic therapeutics are now specializing into sub-domains.
One productive area reflects de-repression. The most mature example being ipilimumab (Yervoy), the monoclonal directed against CTLA-4. This broadly expressed T-cell repressor molecule can be de-repressed resulting in significant anti-tumor activity, but with moderate to severe toxicity. The inhibition of PDL-1 is more selective and therefore less toxic, it has provided responses in melanoma, NSCLC and other diseases.
Earlier stage research is also focusing on tryptophan metabolism and the role of indoleamine 2, 3-dioxygenase. Manipulations of dendritic cells, altering prostaglandin TGF beta, IL-10, IL-6 and the STAT3 signaling pathway are also areas of active investigation. Additional studies included transferred receptors, like the CD19-related chimeric antigen receptor work and the targeting of co-stimulatory molecules like CD28.
Among the most striking observations in this field is the role of the human immune system and the tumor microenvironment in tumor promotion. Immunologists are rapidly learning that cancer is much more than just cancer cells.