Sunday, January 18, 2015

CEACAM1

I find the relatively new trend of patients and families "discovering" new medications and treatments via press releases by companies in business rags, Forbes, etc. rather than medical journals, scientific publications, and their doctors rather disturbing.  Don't get me wrong.  I am all for spreading the news about the next great drug in as many ways and to as many folks as possible.  It's just that when company claims regarding treatments and cures are published as investment propaganda for stockbrokers and market watchers, patients have no way of knowing if the product is REALLY going to be a possible cure or just more snake oil a company is happy to make money on until the ratties prove its effectiveness or....not.

CEACAM1 has made a splash in just this way.  (See the technews link below.)  However, since some folks wrote to ask me about it and it made news on a couple of forums, I decided to try to find out what all the fuss was about.  It wasn't that easy.  In my research I discovered that CEACAM1 is a molecule that affects adhesion of cells to other cells, the formation of blood vessels, and has interaction with lymphocyte function.  It has opposing effects in different cancers.  In breast cancer, it seems that the more you have of it, the better.  In melanoma, the more you have, the worse your prognosis.  In  fact, in melanoma it can be used as a prognostic marker...with greater predictive ability than Breslow levels.  There is some pre-clinical evidence that blocking CEACAM1 with an antibody will enhance t-cell function against the tumor. The only real 'study' I could find was an examination in mice and Petri dishes from 2012 (link also below).

Novel immunotherapy for malignant melanoma with a monocolonal antibody that blocks CEACAM1 homophilic interactions.  Ortenberg, Sapir, Raz, et al.  Mol Cancer Ther. June, 2012.

"CEACAM1 was reported as a strong clinical predictor of poor prognosis in melanoma.  We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. ....we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy.  ...MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does not induce any agonistic effect. We show using cytotoxicity assays that MRG1 renders multiple melanoma cell lines more vulnerable to T cells in a dose-dependent manner...  It is shown that MRG1 reaches the tumor and is cleared within a week.  ...approximately 90% of melanoma specimens are CEACAM1 positive, implying that the majority of patients with melanoma could be amenable to MRG1 based therapy.  ...MRG1 does not directly affect CEACAM1 positive cells.  CEACAM1 blockade is different from other immunomodulatory approaches as MRG1 targets inhibitory interactions between tumor cells and late effector lymphocytes, which is thus a more specific and compartmentalized immune stimulation with potentially superior safety profile."

Regarding the question of upcoming trials:  They are reported to be starting at Yale and UCLA in the first quarter of 2015.  Dr. Ribas is one of the researchers.  There is no posting on clinicaltrials.gov yet.  

technews reports on CEACAM1 

abstract of CEACAM1 study in Molecular Cancer Therapeutics from 2012 

If CEACAM1 inhibition is the next big thing to help melanoma patients...that will be awesome.   Hang in there, ratties.  It may be a crazy ride.  - c

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