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CD47


dumbcritic
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Joined: 5 years ago
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Back in 2000 Dr. Oldenborg and colleagues hypothesised that CD47 served as a marker of 'self.' Specifically, they proposed that the surface expression of CD47 on red blood cells served as a mechanism to prevent macrophage (a type of white blood cell) phagocytosis (ingestion) https://science.sciencemag.org/content/288/5473/2051.long

In immunity this function's as a "don't eat me" signal when it interacts with SIRP-a on macrophages. Cells that have lower levels of CD47 and higher calreticulin (an ''eat me'' signal) are removed by the immune system, whereas cells expressing elevated levels of CD47 are resistant to destruction due to a balance of pro- and anti-phagocytic signals. So in order to avoid phagocytosis by macrophages, cancer cells upregulate CD47. This is observed in many types solid and hematological malignancies. it is a broadly conserved tumour escape mechanism https://www.pnas.org/content/109/17/6662

Here are some trials testing anti-CD47 mAbs https://clinicaltrials.gov/ct2/show/NCT03530683 https://clinicaltrials.gov/ct2/show/NCT02663518 https://clinicaltrials.gov/ct2/show/NCT02890368 https://clinicaltrials.gov/ct2/show/NCT03248479 https://clinicaltrials.gov/ct2/show/NCT02953782 https://clinicaltrials.gov/ct2/show/NCT02953509


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dumbcritic
(@dumbcritic)
Joined: 5 years ago
Posts: 104
Topic starter  

Encouraging data on Gilead's Magrolimab in MDS and AML [1]. Here is a link to the pivotal trial in MDS [2] and another in AML (this is not pivotal, but depending on the overall data from it and a second ongoing one should be open sometime next year) [3].

 

Refs:

1 https://markets.ft.com/data/announce/detail?dockey=600-202005290800BIZWIRE_USPRX____BW5006-1

2 https://clinicaltrials.gov/ct2/show/NCT04313881

3 https://clinicaltrials.gov/ct2/show/NCT04435691

 


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dumbcritic
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Joined: 5 years ago
Posts: 104
Topic starter  

Trillium Therapeutics has update results from early-stage dose-escalation studies of top candidates TTI-621 and TTI-622 [1].

TTI-621 (SIRPa-IgG1 fusion protein): Preliminary data from a four-part PhI open-label trial in patients with relapsed/refractory blood cancers showed that weekly infusions up to 1.4 mg/kg were well-tolerated with no dose-limiting thrombocytopenia (low blood platelets) (response data not yet available). In the 1.0 mg/kg dose arm, there was one complete response and one partial response in six evaluable patients. Two were bridged to allogeneic transplantation. Enrollment in the 2.0 mg/kg cohort is underway [2].

TTI-622 (SIRPa-IgG4 fusion protein): Again, preliminary data from a two-part open-label PhI trial in patients with relapsed/ refractory lymphoma or multiple myeloma showed a 33% (n=6/18) response rate, five partials and one complete, at the first assessment at week eight. There was one serious dose-limiting toxicity (thrombocytopenia) in the 8 mg/kg cohort (six evaluable patients). Clinical responses were observed across a range of lymphoma types. Enrollment in the 12 mg/kg cohort is underway [3].

 

Refs:

1 http://www.globenewswire.com/news-release/2020/09/08/2090436/0/en/Trillium-Therapeutics-Announces-Updated-Data-From-Its-Ongoing-TTI-622-and-TTI-621-Dose-Escalation-Studies.html

2 https://clinicaltrials.gov/ct2/show/NCT02663518

3 https://clinicaltrials.gov/ct2/show/NCT03530683


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