Cancer Vaccines Enter Clinical Trials

dlb823

Sounds like promising work in the area of immunotherapy...

http://lacrossetribune.com/news/local/cancer-vacci...

MusicLover

Deanna, Is it possible for you to copy and paste the article? The text is not available to me, I think I need to pay a fee or something? Do you know how much the fee is? Thank you.

dlb823

ML, I think you just have to answer a couple of questions to access the article, but here it is...

14 hours ago • Blythe Bernhard St. Louis Post-Dispatch

(1) Comments

"I have statistically beaten the odds of what was expected of my survival."
Michelle Ashby, vaccine trial patient

ST. LOUIS — Is the best treatment for cancer already inside of us?

Research is underway at Washington University to test a new approach to cancer treatment. Beyond traditional therapies like surgery, chemotherapy and radiation, scientists want to know if the human body's own immune system can attack tumors.

They're testing personalized vaccines designed to target deadly cancer cells in each patient. A vaccine is any substance that prevents or treats a disease with properties of the disease itself. Scientists know that fighting fire with fire works for many viruses like flu, measles or polio. Now they want to test that theory with cancer, but since every tumor is different, every vaccine will be different.

Advancements in genetic sequencing, or decoding the DNA of cells, have made it easier to figure out what makes tumors unique. Scientists have found potential targets in tumor cells that could cause them to break down. Now they're passing that knowledge on to doctors to try out in their patients with the most challenging cancers. Clinical trials are now enrolling patients with melanoma, brain cancer and breast cancer.

The concept is hypothetical. The research is experimental. There is no proof that it works.

But after staring down deadly cancers, tumors that have spread and patients who are out of options, doctors are intrigued.

For decades, scientists have gone back and forth on whether the immune system — the body's defense mechanism — has anything to do with cancer. In the 1950s a concept called cancer immuno-surveillance took hold, meaning that the immune system could recognize tumor cells as foreign. By the 1970s the theory was rejected after laboratory mice with weak immune systems did no worse than normal mice when they developed cancer.

Most cancer scientists moved on to trying different pharmaceutical routes for new treatments. Robert Schreiber of Washington University wanted to know more about those mice. He started more sophisticated tests with mice that lacked a critical gene that allowed the immune system to make lymphocytes — white blood cells that defend the body against disease.

"What we showed conclusively was mice that had defects in the immune system got tumors more quickly and in higher incidences than normal mice," Schreiber said.

And with that, the concept of cancer immunology was back.

The Center for Human Immunology and Immunotherapy Programs at Washington University launched last year with Schreiber as director to help doctors use the immune system to fight cancer and other diseases.

Other medical centers around the world have taken different approaches to cancer immunology. Duke University is working with a polio virus vaccine to induce the immune system to fight brain tumors. The Mayo Clinic is doing a similar trial with a measles vaccine. Other clinical trials involve reprogramming the immune system's checkpoints that prevent it from attacking certain cells.

Washington University leads the study of personalized cancer vaccines. With help from their genetic sequencing labs, local scientists try to isolate the best antigen targets — or the most dangerous mutated cells — from each patient's tumor to vaccinate against.

Vaccines are typically viewed as preventive, such as flu shots to help avoid flu infection. Cancers known to be caused by viruses can also be prevented this way. The HPV (human papillomavirus) vaccine can prevent some cervical cancers and the hepatitis B shot protects against development of liver cancer caused by that virus.

Scientists now think vaccines can also be used to stimulate the immune system to fight cancers that are already formed. But without a known virus or other cause, scientists must figure out what differentiates a patient's tumor cells from healthy cells. Then they must try to vaccinate against mutations, called neo-antigens, that occur only in the bad cells.

The immune system is a finely tuned machine that is difficult to manipulate. One challenge is turning up a patient's immunity without harming healthy cells, the process that happens in autoimmune disorders like multiple sclerosis. One type of immunotherapy, called checkpoint blockade, is risky because it can backfire and make the patient vulnerable to an overly aggressive or weakened immune response. Cancer vaccines, in theory, could be safer because they activate more highly precise targets.

"The real essence of that vaccine design is picking out the peptides (proteins) that have the strongest interaction with the patient's immune system," said Elaine Mardis, director of technology development at the university's McDonnell Genome Institute. "It's a different answer for every patient."

Melanoma

The first human trial to apply this concept included three patients with melanoma whose cancer had spread to their lymph nodes. After surgeries to remove their tumors, their cancerous and healthy cells were sequenced to identify mutations. The patients received an infusion using cells from their own immune systems. The treatments stimulated the immune system through a boost of protective T-cells.

After 20 years of specializing in treating deadly skin cancers, the results published earlier this year were gratifying for Dr. Gerald Linette, a co-leader of the trial. But he urges patience to those looking for quick answers.

"(We) are still really the only lab that's done this in people, and that's three patients. I think that we have to be very cautious. Time will tell if this is going to work or not," Linette said.

His partner in the trial, Beatriz Carreno, said genetic sequencing technology has sped the process of using mutations to encourage the immune system to fight cancer. They are now expanding the clinical trial to include more patients.

Brain cancer

Brain tumors are particularly challenging for immunotherapy targets because the molecules are more diverse compared to other cancers. And the immune system works differently in the brain than it does in the skin or other areas of the body. Messing with the immune system in the nervous system can lead to paralysis or brain damage.

Genetic sequencing creates a search party for "the Achilles heel in each patient's tumor," said Dr. Gavin Dunn, a neurosurgeon. A clinical trial is underway to test vaccines against the most deadly brain tumors, called glioblastomas. The first patient will get a personalized vaccine in the next few weeks.

"I don't think we make a lot of progress by doing the same things we've done before, and this is something new," Dunn said.

Dunn regularly receives emails from desperate families asking for help for their loved ones. Current treatments for glioblastomas have not changed much in 10 years. With traditional chemotherapy and radiation, the average lifespan after diagnosis remains stuck at 14 months.

"Clinicians and patients and scientists just want to see patients do better," Dunn said. "The extent to which that will improve and the speed in which we will get there is hard to know … but we have to do better than that."

Breast cancer

Dr. William Gillanders led a study in 2010 on a vaccine that used a target called mammaglobin-A, a protein that is expressed in most breast cancers. The vaccine proved to be safe in women who had late-stage breast cancer that had spread to other parts of the body. The women had previously received traditional surgery, chemotherapy and radiation treatments.

Close to half of the 14 patients who received the vaccine had no tumor growth after one year, compared with one-fifth of the 12 patients who did not receive the vaccine.

Michelle Ashby of O'Fallon, Ill., was one of the patients who received the vaccine after she was diagnosed with stage four breast cancer at age 40.

"I knew there needed to be more research on breast cancer and if the study didn't directly give me benefit, I felt confident it would give benefit to my daughter and other people who are struggling with breast cancer," Ashby said.

For the next 5½ years, Ashby had no cancer recurrence. In August, doctors found some cancerous growth in her breast tissue and it was removed surgically.

"I have statistically beaten the odds of what was expected of my survival," said Ashby, now 46.

That initial research on the mammaglobin-A vaccine will be expanded with more patients, and new clinical trials are open to test personalized vaccines for breast cancer.

"Now that we understand that there is this very dynamic interaction between the immune system and cancers," Gillanders said, "a lot of people think that immune responses will be more effective" with personalized vaccines.

Drug companies are not enthusiastic about the idea of personalized medical care that would require a different vaccine for each cancer patient. But new biotech companies are forming to take this approach. Schreiber of Washington University is a co-founder of one of these companies, Boston-based Neon.

Schreiber said that in five years, scientists should have a good idea if cancer vaccine treatments will be ready for general use. A lot of evidence will be required to prove that the immune system can effectively kill off cancer.

Personalized vaccines can't be mass manufactured for pharmacy shelves. But the process of making them can be streamlined, doctors say. The process that wasn't even possible five years ago has now been expedited to a few months from genetic sequencing of a patient's tumor to the injection of the vaccine. The work is a classic example of moving basic science out of the laboratory and into the doctor's clinic.

The looming question is what happens next. Dunn, the neurosurgeon who specializes in the deadliest type of brain tumors, said he believes in the basic science behind cancer vaccines.

"I really want to be measured about the expectations because we just don't know yet," he said. "But I'm an optimist by nature, and I'm extremely hopeful that what we're learning in cancer immunotherapy will really bring us to a place where we can help patients."

"I have statistically beaten the odds of what was expected of my survival." Michelle Ashby, vaccine trial patient

MusicLover

Deanna, You're a sweetie, thank you!

cp418

Now these vaccine are real progress IMO! Thanks for posting!

MusicLover

partyof5 may have been part of this trial, see her post here

https://community.breastcancer.org/forum/8/topics/835802?page=1#idx_15

SelenaWolf

Yep. If they can't come up with a cure, I would happily embrace a vaccine/control.

JohnSmith

I believe this is the breast cancer vaccine trial discussed in the article, which concluded last year.

1. https://www.clinicaltrials.gov/ct2/show/NCT00807781

Title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of a Mammaglobin-A DNA Vaccine in Breast Cancer Patients With Metastatic Disease

The purpose of this study is to evaluate the safety of mammaglobin-A DNA vaccine in metastatic breast cancer patients.

Enrollment: 15
Study Start Date: October 2009
Study Completion Date: December 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

---

I also saw this new MammaglobinA vaccine clinical trial, which is recruiting "Newly diagnosed" ER+, HER2- patients, also being conducted at Washington University in St. Louis, Missouri.
2. https://www.clinicaltrials.gov/ct2/show/NCT02204098

Title: A Phase 1B Randomized Clinical Trial to Evaluate the Safety and Immune Response to a Mammaglobin-A DNA Vaccine in Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy

The purpose of this research study is to find out about the safety of injecting the gene (DNA) for mammaglobin-A into people with breast cancer. The DNA used in this study was purified from bacteria and contains the gene for mammaglobin-A. Mammaglobin-A is a protein that is highly expressed by breast cancer cells. Injection of mammaglobin-A DNA may be a way to generate an immune response to breast cancer cells. There is evidence that an immune response may be a way to fight cancer. In addition to evaluating the safety of the mammaglobin-A injection, this study is also looking at the immune response that the participant's body has after each injection.

Estimated Enrollment: 12
Study Start Date: January 2015
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)

The deleted data above was from March 2016.

As of June 2016, the website has been updated to reflect the following:
Estimated Enrollment: 60
Study Start Date: January 2015
Estimated Study Completion Date: October 2024
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)

StonyPony

I've entered into the Washington University "Safety and Immune Response to a Mammaglobin-A DNA Vaccine In Breast Cancer Patients Undergoing Neoadjuvant Endocrine Therapy" https://clinicaltrials.gov/ct2/show/NCT02204098 . First vaccine appt. is next Thursday.

Currently on Anastrozole 1mg/day Zoladex 1injection/month. Ki67 result after 14 days on hormone treatments <2

Met with PS this morning and moving on to schedule bilateral mastectomy in the next month. (Tumors in both breasts

I'll let you know how it goes if allowed! Fingers crossed!

Moderators

Hi StonyPony! Welcome, and good luck with the trial!!

There are many other threads you may want to join such as For Arimidex (Anastrozole) users, new, past, and ongoing, where members will sure welcome you with open arms.

Let us know when you have more information on your surgery.

Best wishes,

The Mods

StonyPony

Update- 2 weeks post Bilateral Mastectomy with expanders placed under the muscle and 7 lymph nodes removed.

Doing well! My lymph node pathology came back showing only a couple of tiny cells in the first node so I'm awaiting word on whether I will need radiation or not. As of last week I was still the only person to have made it through the 3 rounds of vaccine injections for the study. One other woman qualified to receive the vaccine and she bowed out after the first round. She was older and slightly frail and couldn't take the jolt of electricity that accompanies the injection.

There is a lot of hope and buzz about this trial so I really hope this unlocks the door to wiping out at least one kind of breast cancer! It was funny being the first one through this round of the study. My terrific nurses and I joked and laughed as we worked trough the best way to sit for the injection (Laying down turned out to be the best), and determined that because they alternate between arms and legs each of the 3 months it is better to start in the legs then do arms then back to legs as I found there was less pain in the larger thigh muscles. The manufacturers representative for the delivery tool (the gun) was there for the first set of injections so I got to ask a lot of questions about it. Dr Gillanders was there for the second round but had to leave before the vaccine made it up from the pharmacy. It was great to be able to chat with him about the study. The one question I had was why electricity was used in conjunction with the injection of the vaccine. I work with horses and have some knowledge of how various deliveries of injections work in different ways. Dr. Gillanders said that the electric pulse opens up the cell wall to allow the vaccine to be absorbed into where it is needed. That makes sense to me. It's not the most pleasant thing but if it works then I'll deal with a moment of pain! In the big scheme of my cancer treatment and bilateral mastectomy road it's just a blip.

The only side effect I had from the injection was some bruising and soreness at the injection site which was no different that a tetanus shot. The bruising was the worst the first time and I had no bruising after the last time at all.

I did feel like a bit of a study star having the device rep and the head of the study chat with me! My nurses were definitely stars and became good friends. They presented me with a rainbow "my little pony" and a congratulations balloon on the last day which made me cry! I still see them when I go for my monthly Zoladex injection and lab work so I will keep asking if any others have made it in to the study yet and keep you posted of any developments.

JohnSmith

Excellent post StonyPony.

My old notes indicate that the mammaglobin-A protein is overexpressed in ~80% of Luminal (ER+) breast cancers.
In triple negative, the protein is overexpressed in about 40-50% of cases.

I had a few questions.
1. According to the 'Inclusion Criteria' on the trial website, here, enrollment is for HER2- patients, yet you are HER2+, correct?

2. I assume they did a diagnostic test to determine your expression level of the mammaglobin-A protein. Any idea of what your numbers were (mammaglobin-A expression level), or is this kept confidential by the researchers?

3. This trial has been open since Jan 2015 (according to the trial website), yet you are the first to make it through 3 injections.
Has there been slow accrual (enrollment problems) or did many patients simply drop out of the trial?

4. I didn't realize they used electroporation with the injection.
For those unaware, "Electroporation" is the action or process of introducing DNA or chromosomes into bacteria or other cells using a pulse of electricity to briefly open the pores in the cell membranes.
On a scale from 1 to 10 (10 being the highest), what was the level of pain from electroporation?

Thanks!