Aiming for Immunity: New Therapies in Sights

Anita T. Shaffer
Published Online: Thursday, July 14, 2011
targeted therapyEven before the FDA approved ipilimumab in March, the field of cancer immunotherapy was a lively area of scientific inquiry. Now, experts expect the success of the melanoma drug Yervoy to further draw research attention toward developing ways of helping the human body’s innate defenses fight tumors.

In fact, the breadth and complexity of immunotherapeutic approaches are unfolding as the possibilities mushroom.

The 2011 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, in June provided a plethora of new research, with reports on a variety of vaccines, combinations with standard therapies, and novel strategies to reduce the dysfunction of the immune system.

“We’re going to have an explosion of possible combinations,” Thomas F. Gajewski, MD, PhD, president of the Society for Immunotherapy of Cancer (SITC), said in an interview with OncLive. “It’s going to be a challenge to prioritize those so that the most effective candidates get tested first.

Thomas F. Gajewski, MD, PhD
Thomas F. Gajewski, MD, PhD
“At the same time, that makes it exciting,” added Gajewski, a professor in the departments of Pathology and Medicine, Section of Hematology/Oncology at the University of Chicago Medical Center. “Now that things are starting to click, there’s going to be a lot of work.”

Indeed, Tyler J. Curiel, MD, MPH, a professor of Medicine at the University of Texas Health Science Center in San Antonio, said researchers have much work to do to understand how the immune system breakdown that cancer cells induce can be overcome.

“Right now, we don’t really have a very good understanding of what are the specific immune factors generated by active interventions that would lead to a positive outcome in cancer,” he said during a presentation at the ASCO congress entitled “Progress in Tumor Immunotherapy.”

Tyler J. Curiel, MD, MPH
Tyler J. Curiel, MD, MPH
There are many big questions, he said, starting with defining the critical dysfunctional pathways, cells, and factors. “What are the optimal means to intervene? Who are the ideal patients? How should these strategies be combined?” he asked.

Such questions already are making immunotherapy one of the most active areas of cancer research, with more than 80 possibilities in various stages of discovery, according to the Oncology Business Review, an industry publication.

“Immunotherapy is going to become one of the key treatment modalities in cancer over the coming years,” said Axel Hoos, MD, PhD, medical lead for Yervoy at Bristol-Myers Squibb and co-chair of the executive committee of the Cancer Immunotherapy Consortium, in an OncLive interview.

New Approach Creates Excitement

The ASCO congress was a moment in the spotlight for ipilimumab, not only because it demonstrated the ability to prolong survival in a disease for which no new drug had been approved for more than a decade, but also because of its mechanism of action.

Axel Hoos, MD, PhD
Axel Hoos, MD, PhD
Ipilimumab, which is administered intravenously, is a humanized monoclonal antibody that blocks the cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule from inhibiting antibody response to cancer cells, thus allowing the T cells to proliferate and fend off alien antigens.

The drug takes the brakes off the immune system, said James P. Allison, PhD, chairman of the Immunology Program at the Memorial Sloan-Kettering Cancer Center in New York City, whose discoveries led to the development of ipilimumab.

Related: Independence and Tenacity Anchor Immunology Pioneer: A Closer Look at James P. Allison, PhD

The immune cosignaling blockade approach that ipilimumab employs is among the emerging areas of inquiry. Because ipilimumab treats the tumor and not the specific disease state, the drug has the potential for use against many other cancer types.

“It has broken new ground for cancer immunotherapy in general,” and is a first-in-class agent because of the way it enhances T-cell activation, Hoos said.

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