#cd47

[teddytarnieandme]

Bought some new cheapo PTs yesterday. I much prefer spending $5.20 on 20 tests over $17 on 3 tests 😐 Especially when I have literally no idea what is happening because there's no sign at all of AF. I'll probs test the day after they arrive and if it keeps up I'll be going to see my GP.

I know it can take some sorting out after stopping the pill, but the first two months it was pretty much on time give or take a day or two, and this time I'm at CD47.

[sontoro]

The world’s largest Nixie tube, the Rodan CD47.

[rootsanalysis]

CD-47 Targeting Therapeutics Market report features an extensive study of the current market...

According to the World Health Organization (WHO), at present, cancer is the second leading cause of death, worldwide. The National Cancer Institute (NCI) has estimated that, by 2030, over 22 million individuals are likely to be diagnosed with various types of cancer, in the US alone. As a result of the growing patient population affected by this disease, there is a rise in the demand for effective treatment modalities. The conventional approaches, such as chemotherapy, surgery and radiation therapy, employed for the treatment of oncological indication(s) are considered to be inadequate, specifically for late-stage cancers.

[pharmtastic]

Can Anti-CD47 “cure” cancer?

CD47, a five transmembrane domain, integrin-associated protein that is ubiquitously present throughout the human body. With respect to cancer, CD47 sends a “Don’t eat me” signal to macrophages and therefore considered to be one of the most common mechanisms for aggressive tumor growth. Modulating this signaling pathway has resulted in positive outcomes in almost all cancers studied. (see below)

Dr. Irv Weissman of Stanford Univ. presenting the list of human cancers under study via @CIRMnews 

Hu5F9-G4, the anti-CD47 antibody discovered by Dr. Weissman’s lab and now being developed further by Forty Seven Inc, a spin-off (backed by Google money!). They presented their data from the first-in-human trial in advanced cancers and concluded that Hu5F9-G4 was well tolerated at 3 mg/kg dosing. However, due to the ubiquitous nature of CD47, antibodies targeting this protein are expected to cause a number of side effects including anemia (RBC loss). To compensate for this adverse effect, they used a priming dose of Hu5F9-G4 to occupy all RBC CD47 receptors with “limited” side effects.

So what about the competition?

Obviously, a number of other biotech companies are also working on therapeutics targeting this pathway. Trillium Therapeutics ($TRIL) remains one of their biggest competitors, and are developing a SIRPαFc and human IgG1 Fc fusion protein (TTI-621) to act as a decoy receptor that elicits phagocytosis by macrophages followed by a T-cell response. They recently presented the results from their Phase 1a trail in Diffuse large B-cell lymphoma (DLBCL) and Hodgkin’s lymphoma patients (n=6 each). Make what you will of the data (below) but we can all agree it does not look like a “cure” (at least not as a monotherapy in really aggressive cancers). However, it is a start and it would be interesting to see how it works in combination with current drugs targeting antigens - CD20 (rituximab) in B cell lymphomas or HER2 (trastuzumab) in breast cancer.

Curiously, they managed to avoid binding to CD47 on RBCs and claim that this is due to “lack of CD47 membrane mobility combined with moderate affinity of TTI-621 for target”. However, they observed transient thrombocytopenia in their Phase 1a trial (Data below). Although they downplay this by saying “TTI-621 is generally well tolerated”, they are obviously a little worried about this adverse reaction, hence the development of second generation molecule TTI-622 that, unlike TTI-621, has a human IgG4 Fc fragment. They expect that “TTI-622 is less likely to deplete platelets, enabling higher exposures”.   

Further, they are working on other malignancies including solid tumors with results expected by the end of the year. More recently, they have had one big win by winning against Forty Seven Inc over patent infringement claims (below). 

What about the others?

OSE Pharma ($OSE) is taking the obvious alternate approach by blocking the SIRPαFc receptors on macrophages and hence preventing CD47-mediated “Do not eat me” signals. They claim that EFFI-DEM, an IgG4 specifically targeting SIRPαFc has shown promising data in solid tumor preclinical models. 

Celgene's CC-90002, anti-CD47 antibody licensed from Inhibrx in 2012 and might be the furthest along in the development process. Data from their Phase 1 trials expected at the AACR meeting in April this year. 

Novimmune’s NI-1701, anti-CD47/CD19 bispecific antibody and NI-1801 anti-CD47/Mesothelin bispecific antibodies are in pre-clinical and discovery phases respectively. 

Tioma Therapeutics (formerly Vasculox), a spin-off from William Frazier’s lab at Washington Univ., St. Louis. Interestingly, some of his recent papers show additional applications of anti-CD47 antibodies in organ transplants!  

Alexo Therapeutics, another Stanford spin-off, are developing “high-affinity soluble SIRPα monomers (Alexo compounds)” to block CD47-SIRPα interaction. These monomers are based on (some very cool) work previously reported from the Garcia lab in collaboration with Dr. Weissman et al.

Edit: I forgot to mention that I am invested in both $TRIL and $CELG stocks. 

[kelsiefawn]

When your app doesn't know wtf

Is going on either. My periods are still irregular and every two days my app says your period should start today! And I have to go delete it -_- can't wait for my doctors appt on Monday!

[expectsomuch]

When mice with human tumors received doses of anti-CD47, which sets the immune system against tumor cells, the cancers shrank and disappeared.

Again, what year is it?

[rkrehn-blog-blog]

Scientists at the School of Medicine have shown that their previously identified therapeutic approach to fight cancer via immune cells called macrophages also prompts the disease-fighting killer T cells to attack the cancer.

The research, published online May 20 in the Proceedings of the National Academy of Sciences, demonstrates that the approach may be a promising strategy for creating custom cancer vaccines.

Various researchers have been working over the years to create vaccines against cancer, but the resulting vaccines have not been highly effective. Current approaches to developing the vaccines rely on using immune cells called dendritic cells to introduce cancer protein fragments to T cells — a process known as antigen presentation. The hope has been that the process would stimulate the body’s T cells to identify cancer cells as diseased or damaged and target them for elimination. However, this process often only modestly activates the most potent cancer-fighting kind of T cell, called killer T cells or CD8+ T cells.

The Stanford team discovered that there was another viable vaccine approach, using the macrophage pathway to program killer T cells against cancer. Irving Weissman, MD, professor of pathology and of developmental biology, and his team previously showed that nearly all cancers use the molecule CD47 as a “don’t-eat-me” signal to escape from being eaten and eliminated by macrophages. The researchers found that anti-CD47 antibodies, which can block the “don’t-eat-me” signal and enable macrophages to engulf cancer cells, eliminated or inhibited the growth of various blood cancers and solid tumors.

In the new study, the Stanford team showed that after engulfing the cancer cells, the macrophages presented pieces of the cancer to CD8+ T cells, which, in addition to attacking cancer, are also potent attackers of virally infected or damaged cells. As a result, the CD8+ T cells were activated to attack the cancer cells on their own. “It was completely unexpected that CD8+ T cells would be mobilized when macrophages engulfed the cancer cells in the presence of CD47-blocking antibodies,” said MD/PhD student Diane Tseng, the lead author of the study. Following engulfment of cancer cells, macrophages activate T cells to mobilize their own immune attack against cancer, she said.

- See more at: http://med.stanford.edu/ism/2013/may/cd47.html#sthash.hoyivZqt.dpuf