Category Archives: Research Trends

Cancer Vaccines: Early Beginnings

Vonderheide

Robert Vonderheide, MD, DPhil

At the ACGT anniversary gala in April, Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research and newly appointed Director of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, briefed the audience on the progress of his research using immunotherapy for pancreatic cancer and other solid tumors. ACGT first supported Dr. Vonderheide’s innovative immunotherapy research for brain tumors, in 2003.

Now Dr. Vonderheide aims to develop a cancer vaccine, which may prove applicable to all human cancers. His team has identified an enzyme – Telomerase – present in all cancers. Known as a universal tumor antigen, telomerase has the potential to serve as a homing beacon for the immune system’s killer T-cells. Early trials indicate a robust response, without toxicity, and also measurable survival benefits over time.

A vaccine for cancer? Yes, it is possible, but not quite what you know of a vaccine. A cancer vaccine does not introduce live pathogens into the body; instead, modified genetic material is injected to essentially open the door for the body’s natural immune system to go into action

Vaccination has a long history. The US Vaccine Agency was established in 1813 and predominantly targeted viruses. Polio was subsequently the most prominently known successful vaccination program, in addition to smallpox, measles, influenza, and others that destroyed so many lives.

The first polio epidemic was reported in 1894 and by the early 20th century, hundreds of thousands died every year, mostly children. A virus was identified as the source of the disease, and subsequently three different viruses are known to cause polio. In 1935 the first vaccine trials began, and in 1953, Dr. Jonas Salk gave his vaccine to his own family before approval. By the end of the 1960s, the disease was eliminated in the industrialized nations, and, in the 1970s, routine vaccination was introduced throughout the world. Today, the global incidence of polio is down to 1%.*

Two types of vaccines are used widely to protect against disease, both designed to stimulate the immune system but differently. The polio vaccine is based on Specific immunity – a targeted response to a specific pathogen. An inactivated live pathogen, or segments of the virus, is introduced into the body so the immune system recognizes the threat. A Non-Specific vaccine focuses on what is called Innate Immunity – the body goes on alert to foreign materials. In both cases, the body’s natural killer T-cells are released and regulatory T-cells remain on guard against further invasion.

There are currently two cancer vaccines approved by the FDA: Gardasil and Cevarix. Both cervical cancer vaccines are used to prevent infection with two high-risk HPV strains, which cause nearly 70 percent of cervical cancers. Gardasil is said to prevent infection with the strains that cause nearly 90 percent of genital warts. The CDC recommends these vaccines for girls ages 11 to 12, which allows the immune system to develop antibodies before exposure to HPV.

Dr. Vonderheide envisions a non-specific [Innate] vaccine for cancer, a vaccine using modified genetic material to alert the immune system. It is believed now that all cancers contain a marker – the universal tumor antigen and once all its properties are identified, it will be possible to build a vaccine to seek out and destroy cancer by zeroing in on the antigen, and then remain in the body to protect against any further threats.

We live in a world without polio and it is possible, sooner than you might think, to live in a world without cancer. ACGT Research Fellows are paving the way.

 

*Source: www.polioeradication.org

CRISPR the Next Frontier in Gene Therapy Cancer Research

In our last blog, we described the progress and promise of CAR-T, an immunotherapy that has been particularly successful with leukemia and lymphoma. As a companion to CAR-T, and all forms of cell and gene therapies, CRISPR is the talk of the scientific town these days and is the next tcell_ssfrontier in genetic medicine.

CRISPR. Sounds like something that belongs in your kitchen, doesn’t it? This science is neither therapy nor treatment. It’s a fantastically precise tool that permits genetic editing. Once we completed mapping the human genome, we have the knowledge, and the technology, to effect change in the base DNA that makes up our unique identity. A small change in that code can make a huge difference in health and longevity.

What is CRISPR technology?

Clustered Regularly Interspaced Short Palindromic Repetition is the actual term, should you have an opportunity to prove your medical mettle in conversation. A simpler translation: molecular medical scissors used to repair or replace a portion of the genetic code. #genomics

The technology was discovered just three years ago when researchers, using a DNA cut and paste method using bacteria to protect against viruses, realized they could also edit human genes. In CRISPR, either the cancerous cell, once cut, will repair itself, or the body’s natural killer T-cells will take aim and destroy diseased cells. Unbelievably simple once the barriers caused by mutated or damaged genes are removed.DNA_scissors

Sounds like Sci-Fi? Well, it is a huge leap into the future. So new that scientists from around the world gathered earlier this year for the first international summit on human gene editing, in Washington DC, and agreed to avoid using the science for human genetic engineering. No test tube animals, no Frankenstein. On the other hand, CRISPR is being used to simulate cancers in laboratory animals, for the purpose of study, and much will be learned in this way.

CAR-T, Immunotherapy and CRISPR

CRISPR has the potential to battle not only disease, but also genetic disorders like allergies or neurological dysfunction. The opportunities are limitless. Our own Scientific Advisory Council member, Dr. Carl June, at the University of Pennsylvania, is heading a research team funded by Facebook financier Sean Parker. Dr. June aims to enhance his pioneering immunotherapy by making even more powerful killer T-cells using the CRISPR scissors. Cells will be edited to bypass cancer’s natural protective obstacles to treatment, known as checkpoint inhibitors. [See our blog on CAR-T.]

“This is the first example of CRISPR in clinical trials in humans, period,” Parker reported at the Forbes Philanthropy Summit in August. This sort of advancement may not have been possible without private funding.

 

gene_editing_ssThe race is on to refine the technique. In China, scientists are studying the potential for CRISPR for lung cancer and have secured approvals for first level trials. In the US, the FDA is expected to approve Phase I trials later this year, with patients suffering melanoma, sarcoma and myeloid cancers. The trials will examine toxicity and side effects as well as patient response.

Treating Cancer Patients

Are there challenges? Of course. Medical interventions, even perfected in the lab, must be refined in practice. Humans have been blessed with powerful immune systems that have been too often neutralized when confronted with cancers, but both CAR-T and CRISPR seek to change all that.

The future is happening right now, and ACGT is still the only non-profit in the nation dedicated exclusively to innovative cell and gene therapies for cancer. Stay tuned!

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Witness to Cancer Research Progress

Cancer Moonshot 2020We recently participated in a webinar sponsored by FasterCures featuring highlights of the Cancer Moonshot Summit in Washington, D.C. You may recall the Moonshot is the initiative announced at President Obama’s State of the Union Address in January, and led by Vice-President Biden, to accelerate cancer research in order to improve the ability to prevent and detect cancers, and to build a super highway to more effective treatments by 2020. An unprecedented alliance of medical investigators and pharmaceutical companies has come together to get the job done.

Yes, we’ve heard talk about a war on #Cancer before. However this time, the weight of the White House is behind it, and the program is facilitated by the National Cancer Institute and the National Institutes of Health. So many strides have been made in research in recent years that we hope to see vastly more effective medicines coming sooner to the cancer patients who need it.

An important component of the program is to do a better job matching patients with clinical trials that might save their lives even before final therapeutic approvals, and to do that a government site will serve as the conduit: https://cancerclinicaltrialsideas.cancer.gov/. This is a very important first step.

Greg Simon, Executive Director of the CancerMoonshotTaskForce, reported that the top challenge is to dig deeper into understanding the nature of various cancers and encourage development of new forms of treatment. It is important to encourage greater access to new research data and to break through regulatory barriers, which have been a concern of ACGT scientists all along. He also talked about ensuring optimal investment of federal resources, of course, as well as seeking opportunities for public-private partnerships.

Cancer Moonshot is in Alignment with ACGT’s Mission

Interestingly, these goals line-up with the goals of Alliance for Cancer Gene Therapy and have been our calling card for the 15 years since inception.

Ellen Sigal, founder and chair of Friends of Cancer Research, spoke about the formation of a blue ribbon working panel consisting of 12 groups, each developing recommendations to meet the goals of the Moonshot by the end of this summer. She talked about the importance of cross-fertilization of learning through a national network of clinical and technological data, and we agree, this is terribly important. Too much science happens in isolation and the more we share learning, the greater the results.

ACGT Cancer Research Symposium 2016

She too emphasized the value of public-private partnerships, which was a theme at the ACGT Scientific Symposium in April, where many of our Research Fellows and members of our Scientific Advisory Council are already establishing productive collaborations between the biotechnology industry and the medical research community.

Beyond the general reporting on what needs to be done, which is pretty clear, and what sort of workgroups will get the job done, I also appreciated an increased emphasis on discovery science, where young investigators break new ground – that’s where revolutionary treatments begin and where ACGT has focused more than half our grant funding over the years. Many of those early lab projects are now in clinical trials and/or serve as the basis for new medicines.

While everyone at the Summit is excited for the attention and funding behind the Moonshot, there was serious concern about what might happen after the November election, not only with a new president, but a Congress that has been reluctant to fund such initiatives in spending battles. It would be a shame to halt this initiative as it builds momentum.

Some of the best brains in the country are working together to shake up the system and put revolutionary medical science on a faster track to patients, and ACGT scientists are at the forefront of these efforts, every single day. Stay tuned and learn more. fastercures.tumblr.com