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TNBC MUC1 Vaccine?

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    Posted: Dec 13 2011 at 10:39pm

Scientists develop vaccine that successfully attacks breast cancer in mice


Researchers at Mayo Clinic in Arizona (http://www.mayoclinic.org/arizona/) and the University of Georgia (UGA) have developed a vaccine that dramatically reduces tumors in a mouse model that mimics 90 percent of human breast and pancreatic cancer cases A— including those that are resistant to common treatments.

The vaccine, described this week in the early edition of the journal Proceedings of the National Academy of Sciences (http://www.pnas.org/), reveals a promising new strategy for treating cancers that share the same distinct carbohydrate signature, including ovarian and colorectal cancers.

When cells become cancerous, the sugars on their surface proteins undergo distinct changes that set them apart from healthy cells. For decades, scientists have tried to enable the immune system to recognize those differences to destroy cancer cells rather than normal cells. But since cancer cells originate within the body, the immune system generally doesn’t recognize them as foreign and therefore doesn’t mount an attack.

The researchers used unique mice developed by Sandra Gendler, Ph.D. (http://mayoresearch.mayo.edu/mayo/research/gendler_lab/), the David F. and Margaret T. Grohne Professor of Therapeutics for Cancer Research at Mayo Clinic in Arizona and co-senior author on the study. Like humans, the mice develop tumors that overexpress a protein known as MUC1 (http://discoverysedge.mayo.edu/de08-2-ctsa-gendler/index.cfm) on the surface of their cells. The tumor-associated MUC1 protein is adorned with a distinctive, shorter set of carbohydrates that set it apart from healthy cells.

“This is the first time that a vaccine has been developed that trains the immune system to distinguish and kill cancer cells based on their different sugar structures on proteins such as MUC1,” Dr. Gendler says. “We are especially excited about the fact that MUC1 was recently recognized by the National Cancer Institute as one of the three most important tumor proteins for vaccine development.”

“This vaccine elicits a very strong immune response,” says study co-senior author Geert-Jan Boons, Ph.D., Franklin Professor of Chemistry and a researcher in the UGA Cancer Center and its Complex Carbohydrate Research Center in Athens.

Dr. Gendler says MUC1 is found on more than 70 percent of all cancers that kill. Many cancers, such as breast, pancreatic, ovarian and multiple myeloma, express MUC1 with the shorter carbohydrate on more than 90 percent of cases.

She explains that when cancer occurs, the architecture of the cell changes and MUC1 is produced at high levels, promoting tumor formation. A vaccine directed against MUC1 has tremendous potential to prevent recurrence or as a prophylactic in patients at high risk for particular cancers, Dr. Gendler says. A vaccine also can be used together with standard therapy such as chemotherapy in cancers that cannot be cured by surgery, such as pancreatic cancer.

For the immune system to recognize MUC1 on the tumor cells, it required a special vaccine that had three parts. One part tricks the body into thinking that the cancer cell is a bacterial infection, one part stimulates an antibody response, and one part stimulates a lymphocyte response. If any of the three components were omitted, the vaccine did not work as well.

Dr. Boons notes that MUC1 is also overexpressed in 90 percent of the subset of patients who are not responsive to hormonal therapy, such as tamoxifen or aromatase inhibitors, or the drug Herceptin. These so-called triple-negative tumors are extremely aggressive and difficult to treat, Dr. Boons says, and a new treatment option is urgently needed.

“In the U.S. alone, there are 35,000 patients diagnosed every year whose tumors are triple-negative,” Dr. Boons says. “So we might have a therapy for a large group of patients for which there is currently no drug therapy aside from chemotherapy.”

Dr. Gendler and her colleagues are currently testing the vaccine’s effectiveness against human cancer cells in culture and are planning to assess toxicity. If all goes well, phase I clinical trials to test the safety of the vaccine could begin by late 2013.

###

Co-first authors on the paper are Vani Lakshminarayanan, Ph.D., at Mayo Clinic in Arizona, and Pamela Thompson at the University of Georgia. Additional authors include Margreet Wolfert, Ph.D. and Therese Buskas, Ph.D., both from UGA; and Judy Bradley, Latha Pathangey, Cathy Madsen and Peter Cohen, M.D., all from Mayo Clinic in Arizona.

The research was funded by the National Cancer Institute, the Mayo Breast Specialized Program of Research Excellence (SPORE) Grant and the Mayo Pancreas SPORE Grant.

About Mayo Clinic

Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit www.mayoclinic.org/about/ and www.mayoclinic.org/news.

Contact: Jim McVeigh
mcveigh.jim@mayo.edu
480-301-4222
Mayo Clinic

http://www.breakthroughdigest.com/medical-news/scientists-develop-vaccine-that-successfully-attacks-breast-cancer-in-mice/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Dec 13 2011 at 11:17pm
Hi,

Not sure.......but it looks like there is already a clinical trial at Case Western Reserve with
a muci vaccine.

If anyone knows this is not correct, please correct with a post.

MUC1 Vaccine for Triple-negative Breast Cancer
This study is currently recruiting participants.
Verified on September 2011 by Case Comprehensive Cancer Center

First Received on September 29, 2009.   Last Updated on September 6, 2011   History of Changes
Sponsor:      Case Comprehensive Cancer Center
Information provided by (Responsible Party):     Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:     NCT00986609
Purpose
RATIONALE:
Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer.
PURPOSE:
To evaluate the efficacy of poly-ICLC + MUCI peptide vaccine in boosting the immunologic response to MUCI in patients with triple-negative BC

Condition     Intervention     Phase
Breast Cancer
Inflammatory Breast Cancer
Stage I Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Triple-negative Breast Cancer
Biological: MUC-1 peptide vaccine
Biological: poly ICLC
Biological: MUC1 peptide-poly-ICLC adjuvant vaccine
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: flow cytometry
Phase 0

Study Type:      Interventional
Study Design:     Intervention Model: Single Group Assignment
Masking: Open Label
Official Title:     Pilot Study of a MUCI Peptide and Poly-ICLC Vaccine for Triple-Negative Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Poly iclc Carboxymethylcellulose
U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
Proportion of patients showing an immunologic response [ Time Frame: At week 12 (2 weeks after the 3rd injection) ] [ Designated as safety issue: No ]
Defined as a >= 2-fold enhancement from baseline anti-MUC1 antibody immunity, or for subjects with no antibody to MUC1 at baseline, any detectable antibody immunity against MUC1. To test the hypothesis of a sufficient immunologic response, we will apply a Simon's optimum 2-stage design. The proportion of patients with an immunologic response will be calculated with a 95% confidence interval using method developed for multistage clinical trials.


Secondary Outcome Measures:
Safety and toxicity as assessed by NCI CTC [ Time Frame: Weeks 0, 2, 4, 10, 12, 52, and 54 and then for 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment:     37
Study Start Date:     August 2009
Estimated Primary Completion Date:     August 2012 (Final data collection date for primary outcome measure)
Arms      Assigned Interventions
Arm I: Experimental
Patients receive MUC-1 peptide vaccine subcutaneously and poly-ICLC vaccine intramuscularly in weeks 0, 4, 8, 12, 52, and 56, in the absence of disease progression or unacceptable toxicity. Patients may receive additional vaccines in weeks 34 and 38 if anti-MUC1 immunity falls below the two-fold enhancement from baseline
Interventions:
Biological: MUC-1 peptide vaccine
Biological: poly ICLC
Biological: MUC1 peptide-poly-ICLC adjuvant vaccine
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Other: flow cytometry
Biological: MUC-1 peptide vaccine
Given subcutaneously
Biological: poly ICLC
Given intramuscularly
Other Names:
Hiltonol
poly I:poly C with poly-1-lysine stabilizer
Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
stabilized polyriboinosinic/polyribocytidylic acid
Biological: MUC1 peptide-poly-ICLC adjuvant vaccine
Receive adjuvant vaccination
Other: laboratory biomarker analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: flow cytometry
Correlative studies

Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of MUC1 peptide-poly-ICLC adjuvant vaccine in boosting systemic immunity to MUC1 in women who have completed therapy for AJCC(American Joint Committee on Cancer)stage I-III 'triple-negative' [i.e., ER(-) PR(-) HER2/neu(-)] breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate the safety and toxicity of the MUC1 peptide and poly-ICLC vaccine in this cohort of patients.
OUTLINE:
Patients receive MUC-1 peptide vaccine subcutaneously (SC) and poly-ICLC vaccine SC in weeks 0, 2, and 10 in the absence of disease progression or unacceptable toxicity. Some patients may receive a booster vaccine in week 52. Patients will be followed for study-related Serious Adverse Events (SAEs) for a period of 30 days after their last vaccination. If a patient experiences a SAE while participating in this study, they will be followed until the resolution of the SAE.
Eligibility

Ages Eligible for Study:      18 Years and older
Genders Eligible for Study:      Female
Accepts Healthy Volunteers:      No
Criteria
Inclusion Criteria:
AJCC stage I-III infiltrating adenocarcinoma of the breast who have completed standard adjuvant or neoadjuvant therapy (surgery, radiation, biologic therapy, chemotherapy) for TNBC (ER-, PR-, HER-2/neu-)
Patients who have completed standard therapy for triple-negative inflammatory BC are eligible
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Absolute neutrophil count >= 1,000/mm^3
Hemoglobin >= 10.0 g/dl
Platelet count >= 100,000/mm^3
Total bilirubin must be within normal limits
Transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) may be up to 2.5 x institutional upper limit of normal (ULN) if alkaline phosphatase is =< ULN
Alkaline phosphatase may be up to 4 x ULN if transaminases are =< ULN
Normal creatinine and blood urea nitrogen (BUN); if abnormal, calculated creatinine clearance must be >= 60 mg/dL
Human immunodeficiency virus (HIV)(-), antinuclear antibody (ANA)(-), hepatitis panel (-), normal thyroid function tests; these tests will be performed at the discretion of the Investigator if warranted by history or clinical presentation
Patients must be disease-free of prior invasive malignancies for >= 5 years, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
All patients must have completed surgery with sentinel and/or axillary lymph node dissection according to participating institutional guidelines
All patients must have completed adjuvant radiation therapy according to participating institutional guidelines
All patients must have completed either adjuvant or neoadjuvant chemotherapy according to participating institutional guidelines; the choice of chemotherapy is at the discretion of the treating physician
Women of childbearing potential must have a negative pregnancy test and must be willing to consent to using an accepted and effective barrier form method of contraception during participation in the study and for a reasonable period thereafter
Patients must provide written informed consent
Exclusion Criteria:
Known metastatic BC
Radiotherapy, chemotherapy, biologic therapy, or other investigational therapy within the preceding 4 weeks
Previous splenectomy or radiotherapy to spleen
Coexisting or previous malignancies except carcinoma in situ of the cervix or basal cell carcinoma of the skin
Active or uncontrolled infection
Psychiatric, addictive, or any disorder that compromises the ability to give informed consent to participate in or to comply with the requirements of the study
Concurrent systemic corticosteroid treatment - must be off all steroids for at least 4 weeks prior to vaccine administration
Any condition or behavior that in the judgment of the Investigator, would compromise the patient's ability to participate in the study
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00986609

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center     Recruiting
Cleveland, Ohio, United States, 44106
Contact: Joseph Baar     216-844-8683     joseph.baar@uhhospitals.org    
Principal Investigator: Joseph Baar            
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator:     Joseph Baar, MD     Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

With positive thoughts,

Grateful for today...........Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Dec 13 2011 at 11:33pm
Hi,

Just found there was a prior topic on the TNBC vaccine clinical trial (Muci vaccine) started by
Eliza 500 back in 2/2/11.

http://forum.tnbcfoundation.org/tnbc-vaccine-clinical-trial_topic7920_page4.html


Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 14 2011 at 7:53am
Judy,

There was another trial targeting MUC1, but that trial has been put on hold.  You found the other thread talking about that.  Many of us were frustrated because our oncs and our members contacted Dr. Barr and no one would get a response.  I almost posted this article in that thread, but I consider this new research a totally different trial and research independent of the other one.

Originally posted by 123Donna 123Donna wrote:

OK, I think this is the reason we've not heard much about this trial.

http://www.wkyc.com/news/article/205986/7/UH-doctor-works-on-Triple-Negative-breast-cancer-vaccine

In 2008, Dr. Barr, an oncologist at University Hospitals, tried developing a vaccine that allows one's own immune system to pinpoint and kill cancer cells for women who have suffered Triple Negative breast cancer.

Dr. Barr found a link between this type of cancer and a protein called MUC-1. This discovery green-lighted a study that focused in on protein in breast cancer cells.

The vaccine would prevent a reoccurrence of Triple Negative breast cancer.

In October 2010, the first vaccine was administered and none of the patients developed immunity, however, flu-like symptoms, along with joint discomfort, was a common complaint and Barr decided to place the study on hold.

Dr. Barr has made some changes to the study and hopes to begin a new phase in the future.

"We are keeping our fingers crossed at this one," he said.

WKYC-TV



Edited by 123Donna - Dec 14 2011 at 8:46am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 14 2011 at 8:48am
Judy,

What's frustrating to me is that this new research, if all goes well, could lead to Phase 1 clinical trials by late 2013.  We need something now that works for TNBC.  Sigh. . .

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Wade Quote  Post ReplyReply Direct Link To This Post Posted: Dec 14 2011 at 10:12am
Thanks for rooting this out, Donna. It's always exciting to read that something is happening on TNBC research.

Wade
Wife DX 5/2011@52 2.5x3.1cm;6/2011 DD A/C 4x,Abraxane 4x; Lumpectomy, SN biopsy 10/2011; 10/27/2011 NED; Rads start 11-22-2011, Rads fin 1-11-2012; 10-2013 NED; 07-18-2014 NED; November 2018 NED
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: Dec 14 2011 at 10:51am
This seems to be basing things on the 3 part system of attack. I was intrigued to know how oncs would deal with using this...I would assume they would forego any surgery until after chemo...and since chemo is known to compromise one's immune system, would that impact the vaccine's ability to get the optimum attack from our immune system. And while on the combo of the chemo, the vaccine and still having cancer wouldn't the patient be in pretty severe physical threat from infections, etc?
   2013 is harsh for us, but it's not to say that if the work is recognized that a fast track system won't be allowed.
   Since they've initiated the global joint venture of resolving cancer this year and now put a date on actually finding cures for cancer I won't be surprised if we see alot more fast tracking. Now, if we can just keep the funding flowing as well...no more wars for a bit pretty please.
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
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