Dr. Jeffrey Wasser

Melanoma Patients Benefit from New Immunotherapy Drug

Microscopic view of a histology specimen of melanoma on human skin tissue

Microscopic view of a histology specimen of melanoma on human skin tissue.


Patients with advanced melanoma are benefiting from the same drug credited recently with the disappearance of the disease in former President Jimmy Carter.

Physicians with UConn Health’s Carole and Ray Neag Comprehensive Cancer Center are successfully boosting the immune system of some of their advanced melanoma patients with a new, promising immunotherapy tool called Keytruda (pembrolizumab).

The drug was granted accelerated FDA approval in September 2014 for the treatment of melanoma patients who no longer respond to other drug treatments and are not candidates for surgery.

Melanoma is one of the deadliest types of skin cancer. If not detected early and removed from the skin, it can spread deep into the skin and to the body’s other organs, such as the lungs, liver, and brain. It is often fatal.

“Melanoma affects the young and the old, and its incidence is on the rise,” says Dr. Upendra P. Hegde, associate professor in the Department of Medicine, and chief medical oncologist for melanoma and cutaneous oncology and head and neck cancer/oral oncology at UConn Health. More than 75,000 people are diagnosed with melanoma annually, and nearly 10,000 Americans die from it each year.

Hegde says melanoma spreads quickly because tumors evade the immune system’s attack by expressing proteins called PD-L1 and PD-L2 (program death ligand 1 and 2), compromising the ability of a person’s T-cells to fight cancer.

However, Keytruda boosts a patient’s immune system, helping it fight back and preventing the cancer-fighting cells from becoming exhausted.

“Keytruda is the first PD-1 inhibitor drug that is allowing us to shrink the melanoma tumors in up to 35 percent of our UConn Health patients,” says Hegde.

Since not all advanced melanoma patients respond to current available drug therapies including Keytruda, UConn Health researchers are participating in two clinical trials that combine Keytruda with other therapy options. One, called INCYTE and led by principal investigator Dr. Jeffrey Wasser, is testing the efficacy of combining Keytruda with another immunotherapy drug known as an IDO1 inhibitor (INCB024360) to see if together they can enhance the immune system’s response to advanced melanoma and other solid-tumor cancers. A second trial is testing the possible benefits of Keytruda with standard chemotherapy for relapsed head and neck cancer.

UConn Health’s multidisciplinary melanoma team includes Dr. Jane Grant-Kels and Dr. Philip Kerr of dermatology, Hegde of medical oncology, and Dr. Bruce Brenner, a surgeon who specializes in melanoma, among others.

Individualized

By Lauren Woods
Illustration by Yesenia Carrero

UConn Health’s Personalized Ovarian Cancer Vaccine Enters Clinical Trials

illustration of fingerprints overlayed on top of a woman's ovaries


Ovarian cancer relapses are deadly. UConn Health is testing its pioneering vaccine that could prevent them.

The experimental vaccine, named OncoImmunome, is administered as a simple injection in an outpatient setting. It works by boosting the patient’s immune response to enable it to destroy ovarian cancer cells, so that they do not resurface.

The genetic differences between the surface proteins on a patient’s healthy and cancerous cells constitute the fingerprint of that particular patient’s cancer, which is unlike the fingerprint of any other person’s cancer. Based on these variations, scientists create the personalized vaccine.

“This is the first vaccine of its kind developed for women diagnosed with advanced ovarian cancer,” says Dr. Pramod K. Srivastava, the vaccine’s developer, who is a leading cancer immunotherapy expert and director of the Carole and Ray Neag Comprehensive Cancer Center at UConn Health. “The personalized vaccine is specifically created using a patient’s own genomics information to prevent an often life-threatening recurrence of the disease and extend survival.”

There is no early-screening test for ovarian cancer. When a woman with the disease starts to actually experience non-specific abdominal symptoms such as bloating, the disease has often already advanced to stage III or stage IV cancer. Further, there is no effective long-term treatment for ovarian cancer. Even after a woman is successfully treated with traditional surgery and chemotherapy, the disease has a very high recurrence rate within just two years. Tragically, most women die within five years of their diagnosis.

But Srivastava believes that appropriate immunotherapy may stop an ovarian cancer diagnosis from becoming a death sentence.

“There is a huge need for a therapy to actually prevent recurrence in these women and I believe our approach to a vaccine may be just the tool to do it,” says Srivastava.

In October 2014, Srivastava published a study showing that his promising approach to cancer vaccines is effective in reducing tumor growth and in preventing cancer progression in mouse models. Based primarily on that work, the FDA approved testing of the experimental therapy in a human clinical trial.

The individualized vaccine is created using samples of a patient’s own DNA from both her unhealthy cancer cells and her healthy blood cells. Over a period of about two weeks, scientists sequence and cross-reference the entire DNA from both sources to pinpoint the most important genetic differences. These genetic differences constitute the ID card, or fingerprint, of that particular patient’s cancer, which is unlike the ID card or fingerprint of any other person’s cancer. Based on the cancer’s fingerprint, bioinformatic scientists, led by Ion Mandoiu of UConn’s School of Engineering, design the personalized vaccine that is meant to target the cancerous cells’ specific genetic mutations.

UConn Health’s new clinical trial will initially enroll 15 women with stage III/IV ovarian cancer and track them closely for two years, the window of time when recurrence most often occurs. Candidates for the clinical trial are women recently diagnosed with advanced ovarian cancer who will have traditional surgery and receive chemotherapy. If cancer-free three months after traditional treatment, the women will receive their personalized vaccine injections once a month for six months. Also, each month their blood will be drawn and evaluated for immune response.

“Our clinical trial will be testing the vaccine for safety and feasibility, but also will be testing whether the vaccine is making a real difference in patients’ blood; the timing of recurrence of cancers in these patients will also be monitored,” says Srivastava. “If, after receiving the vaccine, their cancer hasn’t recurred for a long time in a substantial proportion of women, we will know that the vaccine is promising.”


lab image of Ovarian Cancer cells

This UConn lab image shows how the new ovarian cancer vaccine works. Tiny immune cells known as lymphocytes (small purple dots) target and attack the cancerous ovarian cancer growths (outlined in blue) and prevent them from spreading to benign tissue (pink). Lab image courtesy of Dr. Pramod K. Srivastava


In October 2014, Srivastava published a study showing that his approach to cancer vaccines is effective in reducing tumor growth and in preventing cancer progression in mouse models. Based primarily on that work, the FDA approved testing of the experimental therapy in a human clinical trial.

Dr. Angela Kueck, assistant professor of gynecological oncology, and Dr. Jeffrey Wasser, assistant professor of medicine at the Carole and Ray Neag Comprehensive Cancer Center, are the principal and co-investigators of this study.

“We have received over a hundred messages from women in Connecticut and from around the world, in the hope of participating in our study,” says Srivastava.

He adds, “The most meaningful part of my life, at this time, is to serve. I hope that our results a few years from now will show that our unique ovarian cancer vaccine can prevent recurrence of the disease and even extend survival.”

If the clinical trials are successful against ovarian cancer, Srivastava plans to expand testing of his vaccine to bladder cancer and other solid-tumor cancers.

“This first-ever genomics-driven personalized vaccine has the potential to dramatically change how we treat cancer,” says Srivastava.