Immunology and Biotherapies

As of today, there are a total of 367 monoclonal antibodies either on the market or in development. 124 are fully human, 146 are humanized, 37 are chimeric, and 56 are murine, or mice antibodies. Of these 367, 38 are FDA approved since the first got through in 1986. 16 of those 38 have been approved in the last 5 years alone, which translates to 42%. We are gaining traction quickly, it seems.

 

Of the 38 approved mabs, 18 are humanized, 14 are fully human, 7 are chimeric, and only one is murine. The difference between the types is this: A chimeric mab is a cross between an animal and a human antibody engineered to react in a human setting. Humanized means that the antibody is mostly converted into a human form but originally came from an animal, usually a mouse. The term "fully human antibody" though is actually a bit misleading because in almost all cases it is not actually taken from a human. It is generally taken from a mechanism called a phage display, where human antibody genes are injected into a phage virus, which then expresses the antibodies on its coat. The best ones are then harvested from the virus. Think of it as microbiological agriculture.

 

Zooming back out to mabs in general, the top 10 bestselling mabs in 2014 account for $68B of the $78B total mab market last year. Number 1 is the fully human adalimumab, or Humira for rheumatoid arthritis, which looks set to eventually overtake Lipitor as the biggest blockbuster drug of all time. Humira was discovered via phage display, along with (nearly) all other fully human mabs on the market or in development.

Via Krishan Maggon

Abstract

Cytomegalovirus (CMV) is a virus that causes chronic infections in a large set of the population. It may cause severe disease in immunocompromised individuals, is linked to immunosenescence and implied to play an important role in the pathogenesis of cardiovascular diseases and cancer. Modulation of the immune system's abilities to manage the virus represent a highly viable therapeutic option and passive immunotherapy with polyclonal antibody preparations is already in clinical use. Defined monoclonal antibodies offer many advantages over polyclonal antibodies purified from serum. Human CMV-specific monoclonal antibodies have consequently been thoroughly investigated with respect to their potential in the treatment of diseases caused by CMV. Recent advances in human antibody technology have substantially expanded the breadth of antibodies for such applications. This review summarizes the fundamental basis for treating CMV disease by use of antibodies, the basic technologies to be used to develop such antibodies, and relevant human antibody specificities available to target this virus.

Via Krishan Maggon

Highlights

 

•

First time demonstrating that CD47 blockade has anti-tumor effects against HCC.

•

In vitro CD47 blockade results in increase in phagocytosis of HCC cells.

•

In vivo CD47 blockade inhibits HCC tumor growth in hetero/orthotopic models.

•

CD47mAb400 is clearly more efficacious than widely-investigated B6H12 antibody.

 

Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.

Via Krishan Maggon