CD47 Research at Stanford

Good questions. First, lets explain how this Immunotherapy (Anti-CD47) works.
One way cancer cells avoid being killed by the immune system is by over-expressing the CD47 "don't eat me" signal. All cancers use this trick to hide from the immune system. Scientists created an antibody that interferes with this signal and in the process, alerts immune system cells (Macrophages and Dendritic cells) to destroy the tumor cells.

Anti-CD47 is a Monoclonal Antibody (mAb) / immune checkpoint inhibitor that has the potential to benefit ALL cancers, not just breast cancer. What makes this treatment novel is that it targets cancer stem cells (which are theorized, by some, to be the root of all evil), and it also targets the heterogeneous bulk of bad cells that make up a tumor. The CD47 protein is over-expressed in nearly all cancers, making it a unique target.

Stanford University is pursuing anti-CD47 therapies through a non-commercial entity (CIRM grant... i.e. California Institute for Regenerative Medicine, essentially a publicly funded Stem Cell research). The success of this effort has resulted in clinical trials as well as a new company called "Forty Seven, Inc", which raised $75 million dollars to commercialize this Immunotherapy approach.

Here's a couple links describing the project:
CIRM Grant info: Clinical Investigation of a Humanized Anti-CD47 Antibody in Targeting Cancer Stem Cells in Hematologic Malignancies and Solid Tumors

Development of Therapeutic Antibodies Targeting Human Acute Myeloid Leukemia Stem Cells

In addition to Stanford, here's other companies pursuing Anti-CD47 Immunotherapies:
1. ** Celgene (the Anti-CD47 drug is licensed from Inhibrx).
Pipeline: INBRX-103 CD47 mAb
Phase 1 Trial: Dose Finding Study of CC-90002,in Subjects With Advanced Solid and Hematologic Cancers
Trial started Q1 2015 and ends Q4 2017 and it is recruiting breast cancer patients!
2. ** Novimmune - Based in Switzerland. [bispecific anti-cd47 / anti-cd19 antibody]. Here's a June 2015 ASCO abstract. Pipeline: NI-1701
3. ** Trillium Therapeutics (Ticker: TRIL), Toronto Canada. Pipeline: TTI-621.
Phase 1 trial is called: "A Phase 1a/1b Dose Escalation and Expansion Trial of Single-agent TTI-621, a Novel Biologic Targeting CD47, in Subjects With Relapsed or Refractory Hematologic Malignancies" The trial started Jan 2016 and focuses on advanced Lymphoma. They previously indicated AML (Leukemia) & MDS (bone marrow). Preclinical data additional indications include Breast Cancer, among many other solid and liquid tumors.
4. Vasculox - A startup in St. Louis, Missouri - Working on Novel Anti-CD47 Therapeutics. Honestly, this company doesn't look very impressive. Weak funding, weak management team; although one of the early pioneers of CD47 is associated with the company. They've been around since 2006 and still don't appear to have a drug pipeline.
5. Paradigm Shift Therapeutics in Rockville, Maryland. PSTx was launched in Jan 2014 by Teresa Burgess, PhD and Kate Farrell, PhD through an ongoing collaboration with Dr. David Roberts at the National Cancer Institute (NCI) focused on developing CD47-targeting inhibitors-a novel immune-checkpoint target with the potential to radically change treatment for cancer patients.
PSTx is unique since they are focused on Metastatic Breast Cancer using a drug called "PSTx-23".
6. Alexo Therapeutics - A startup near San Francisco, California. Alexo closed Series A funding of $36M in May 2015, which was led by venBio and joined by Lightstone Ventures, the Longevity Fund, and Stanford University.
7. Forty Seven, Inc. - This is the official Stanford "spin-out" startup based in Palo Alto, California. In Feb 2016, they completed Series A financing of $75 million, which was led by Lightspeed Venture Partners and Sutter Hill Ventures with participation from Clarus Ventures and GV (formerly Google Ventures). The lead program Hu5F9-G4 (Anti-CD47) is a monoclonal antibody against the CD47 receptor, a "don't eat me" signal that cancer cells commandeer to avoid being ingested by the immune system. The founders include: Irv Weissman, Ravi Majeti, Mark Chao and Jens Volkmer, all have been involved with CD47 since its discovery at Stanford many years ago.

** The first three have started Phase 1 clinical trials (last updated Feb 2016).

In terms of Stanford, here's a 15 minute video presentation, released in April 2015, titled:
"The Promise of Immunotherapy: Anti-CD47. Monoclonal Antibody Treatment on the Cusp of Revolutionizing Cancer Care".
Dr. Samuel Cheshier, MD PhD, Assistant Professor of Pediatric Neuroseurgery at Stanford, discusses his work on immunotherapy as a possible cure for cancer. It's focused on pediatrics, but the illustrations in the video are helpful for those who don't understand the science.

Finally, Dr. Irv Weissman, who runs the Weissman Lab at Stanford is a juggernaut behind Anti-CD47 therapy.
Here's a June 2015 video discussing Stem Cells and CD47.

** As of June 2017, here are the "Anti-CD47" immunotherapy Clinical Trials:

1. Phase I Trial of Hu5F9-G4 (Hematologic Malignancies or Solid Tumors)
https://clinicaltrials.gov/ct2/show/NCT02216409
This trial is still accepting breast cancer patients. Phase II trials may start in late 2017, depending on the success of the Phase I study.
Sponsor: Forty Seven, Inc. (Stanford University spinoff)
Drug: Hu5F9-G4
Estimated Enrollment: 96
Study Start Date: August 2014
Estimated Primary Completion Date: August 2017
Location: California

2. CAMELLIA: Anti-CD47 Antibody Therapy in Relapsed/Refractory Acute Myeloid Leukaemia
https://clinicaltrials.gov/ct2/show/NCT02678338
Sponsor: Forty Seven, Inc. (Stanford University spinoff)
Drug: Hu5F9-G4
Estimated Enrollment: 30
Study Start Date: November 2015
Estimated Primary Completion Date: January 2018
Location: United Kingdom (UK)

3. Trial of TTI-621 for Patients With Hematologic Malignancies
https://clinicaltrials.gov/ct2/show/NCT02663518
Sponsor: Trillium Therapeutics
Drug: TTI-621
Estimated Enrollment: 270
Study Start Date: January 2016
Estimated Primary Completion Date: June 2019
Locations: California, Colorado, Minnesota, New York, Tennessee

4. Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers
https://clinicaltrials.gov/ct2/show/NCT02367196
This trial accepts breast cancer patients.
Sponsor: Celgene
Drug: INBRX-103 (CC-90002)
Enrollment: 100
Study Start Date: March 2015
Estimated Primary Completion Date: January 2018
Locations: Arizona (Scottsdale Healthcare Research Institute), California (University of California San Francisco: Lead researcher is Dr. Pamela Munster), Texas (South Texas Accelerated Research Therapeutics)

5. Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)
https://clinicaltrials.gov/ct2/show/NCT02641002
Sponsor: Celgene
Drug: INBRX-103 (CC-90002)
Enrollment: 78
Study Start Date: February 2016
Estimated Primary Completion Date: July 2019
Locations: Arizona, Connecticut, Illinois, Massachusetts, New York

6. Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors
https://clinicaltrials.gov/ct2/show/NCT02890368
This trial accepts breast cancer patients.
Sponsor: Trillium Therapeutics
Drug: TTI-621
Enrollment: 54
Study Start Date: October 2016
Estimated Primary Completion Date: December 2018
Locations: California (City of Hope National Medical Center), Oregon (Oregon Health & Science University), Pennsylvania (University of Pittsburgh), Washington (University of Washington Seattle Cancer Care Alliance)
This is for patients with: Solid Tumors, Breast cancer, Mycosis Fungoides, Melanoma, Merkel-cell Carcinoma, Squamous Cell Carcinoma, Human Papillomavirus-Related Malignant Neoplasm, Soft Tissue Sarcoma

7. Study of ALX148 in Patients With Advanced Solid Tumors and Lymphoma
https://clinicaltrials.gov/ct2/show/NCT03013218
Sponsor: Alexo Therapeutics
Drug: ALX148
Enrollment: 110
Study Start Date: January 2017
Estimated Primary Completion Date: December 2019
Locations: Colorado (University of Colorado Denver), Connecticut (Yale University), Michigan (START-Midwest, Grand Rapids)
This is for patients with: Solid Tumors.

8. Trial of Hu5F9-G4 in Combination With Rituximab in Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
https://clinicaltrials.gov/ct2/show/NCT02953509
Sponsor: Forty Seven, Inc. (Stanford University spinoff)
Drug: Hu5F9-G4
Estimated: 72
Study Start Date: November 2016
Estimated Primary Completion Date: December 2019
Locations: California (Stanford University), California (City of Hope National Medical Center), Illinois (University of Chicago), Missouri (Washington University School of Medicine), Tennessee (Sarah Cannon Research Institute)

9. Trial of Hu5F9-G4 in Combination With Cetuximab in Patients With Solid Tumors and Advanced Colorectal Cancer
https://clinicaltrials.gov/ct2/show/NCT02953782
This trial accepts breast cancer patients.
Sponsor: Forty Seven, Inc. (Stanford University spinoff)
Drug: Hu5F9-G4
Estimated: 112
Study Start Date: November 2016
Estimated Primary Completion Date: May 2018
Locations: Michigan (START Midwest), Texas (START Center for Cancer Care), Tennessee (Sarah Cannon Research Institute)

ML, I'm not sure my post really helps. If anything, it's "information overload" for most people.

It sounds to me like you're a step ahead of anyone with this research, since you've had email exchanges with Stanford.

If it's not too soon, ping Stanford again and ask for an update. At some point in the future, I'll fire off an email as well.

JS, Thank you. I understand the premise with anti-CD47, I just wonder if there is a real possibility for a cancer cure and I stay hopeful that there is.  But some times when I listen to or read things about this it sounds like they are so positive and then they say something like this treatment will work well with other treatments as the gentleman mentioned on one of the videos that you attached. It makes me wonder if this is supposed to be one and done or is this another treatment that will be offered to stage IV patients? and then how long will it work?  That would be ok but it crushes my hopes for it being curative. Like you said only time will tell.  I contacted the following gentleman via email:

Christopher Vaughan

Communications Officer

E-mail: 

vaughan1@stanford.edu

JS, From that link to Oncotarget I needed to search on CD47 to find the abstract that you described they also had an abstract involving breast cancer and CD47 but I can't manage to make much sense of what they are saying or I'm just too tired right now to even try.

Thank you again.

To answer the OP's question: Stanford University should be done with the Phase I trial within the next 12 months. They are not accepting new patients.

In terms of Anti-CD47 antibody programs at Celgene and Novimmune...

Celgene initiated their CD47 Phase 1 Trail: "Dose Finding Study of CC-90002,in Subjects With Advanced Solid and Hematologic Cancers".
It started Q1 2015 and ends Q4 2017.

Novimmune is based in Switzerland.
Here's their CD47 abstract from a couple weeks ago from the 2015 ASCO meeting in Chicago. I assume they are further behind. It's Switzerland, so no clue of how that translates to the US and the FDA.

Bottom line: Stanford is ahead of Celgene in the CD47 life-cycle.
Stanford's Phase 1 should be done between Q2 & Q3 2016 vs. Q4 2017 for Celgene's Phase 1.

For future reference, instead of "CD47", Stanford University is using the term "Hu5F9-G4" for their clinical trial. I believe that's the name for the specific antibody they created. If you try & search "Stanford & CD47", for example, you won't find anything new or relevant (most likely).
Anyway, here's a link to the actual trial: Phase I Trial of Hu5F9-G4 which should be done within 12 months.

I don't imagine we have many European members, but this news just hit my radar.

The Ukrainian Cancer Centre of Monoclonal Therapy is conducting a multi-location
Phase 1 trial of Anti-CD47 for Breast Cancer.

It's called: Phase I, Dose-escalating, Clinical and Pharmacokinetic Study of Humanized Сhimeric Anti-CD47 Antibody in Patients With Verified Diagnosis of Breast Cancer ( ASSIST-II )

Estimated Enrollment: 99
Estimated Study Completion Date: September 2016

As far as I know, the trials at Stanford, Celgene and Trillium Therapeutics don't include any breast cancer patients,
so this is unique.

Current locations include centers in: Ukraine, Russian Federation, Romania, Poland, Germany & Czech Republic.

https://clinicaltrials.gov/ct2/show/NCT02488811?te...

https://clinicaltrials.gov/ct2/show/NCT02447354?te...

CD47 / TNBC research done at the NIH (National Institutes of Health) in April 2015.
"Role of CD47 in triple negative breast cancer (TNBC)"

It essentially says that this novel mechanism makes CD47 blocking antibodies (Anti-CD47) an attractive therapeutic candidate for treating triple negative breast cancer.

I just learned that Stanford has one breast cancer patient participating in their Phase 1 trial. I'm not surprised since Anti-CD47 therapies have broad applicability among all cancers. While this is good news, here's better news.
There is an independent Phase 1 trial sponsored by the big pharma company "Celgene" which is testing its Anti-CD47 mAb (licensed from Inhibrx). That trial is called "Dose Finding Study of CC-90002,in Subjects With Advanced Solid and Hematologic Cancers" and found here.
One of the participating trial locations includes the University of California at San Francisco (UCSF).
Dr. Pamela Munster, a UCSF breast cancer specialist, is the lead researcher for this trial site.
It's possible that numerous breast cancer patients can enroll in the San Francisco-based Celgene trial.

Considering that CD47 is one of the most compelling immunotherapies, it may be wise for Stage 4 folks to explore this option.

JS, Thank you.

^{lmwl, Me too! Cure!!!}

The following Abstract elucidates a molecular mechanism of CD47 in breast cancer.

HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells.
Proc Natl Acad Sci USA. 2015 Oct 28. pii: 201520032. [Epub ahead of print]

Authors: Zhang H 1, Lu H 2, Xiang L 2, Bullen JW 2, Zhang C 2, Samanta D 2, Gilkes DM 3, He J 4, Semenza Gregg L 5.

Author info:
1 Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
2 Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
3 Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
4 Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China;
5 Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 gsemenza AT jhmi DOT edu.

Abstract: Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription of the CD47 gene in hypoxic breast cancer cells. Knockdown of HIF activity or CD47 expression increased the phagocytosis of breast cancer cells by bone marrow-derived macrophages. CD47 expression was increased in mammosphere cultures, which are enriched for cancer stem cells, and CD47 deficiency led to cancer stem cell depletion. Analysis of datasets derived from thousands of patients with breast cancer revealed that CD47 expression was correlated with HIF target gene expression and with patient mortality. Thus, CD47 expression contributes to the lethal breast cancer phenotype that is mediated by HIF-1.

KEYWORDS: antitumor immunity; immune evasion; tumor microenvironment; tumor-initiating cells; "don't eat me" signal (CD47), HIF-1

The Abstract title sums it up pretty well.
In this breast cancer study, HIF1A controls the expression of CD47. Over-expression is bad.

HIF1A is implicated in promoting tumor growth and metastasis in most human cancers.
I don't think science has had any success in targeting HIF1A. Perhaps Anti-CD47 therapies are a solution to the HIF1A problem. They'd do this by interfering with the "do not eat me" signal, allowing the Immune system scavengers (macrophages) to do their job and gobble up (phagocytosis) tumor cells. Think Pacman.