The First Use Of A Live Listeria Cancer Vaccine In Humans

Main Category: Cancer / Oncology
Also Included In: Cervical Cancer / HPV Vaccine;  Immune System / Vaccines
Article Date: 16 Apr 2008 - 3:00 PDT

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Phase I/II trial results have shown that the live Listeria cancer vaccine, Lovaxin C, is safe for humans. In addition, three women in the cervical cancer trial had approximately 20 percent tumor reductions, researchers report.

"We are using Listeria to deliver tumor-specific antigens to the immune system in a manner that results in maximal immune and tumor-clearing response," said John Rothman, Ph.D., vice president of clinical development at Advaxis, which is developing Lovaxin C.

The trial included 15 women with progressive, recurrent or advanced cervical cancer. All patients had failed chemotherapy, radiotherapy or surgery. The women had metastatic disease and most were stage IVb.

Listeria monocytogenes infects antigen presenting cells (APCs) - "a very special piece of immune real estate," Rothman said. These cells consume foreign invaders and instruct the immune system to attack them. Listeria thrives within APCs and thus directs an immune response.

"We bioengineer Listeria both to attenuate it and to cause it to secrete a tumor-specific antigen fused to a listerial protein, which makes it more effective than Listeria that just secretes the tumor antigen," Rothman said. "By doing this we focus a very strong immune attack against the antigen in question, which is typically specific to a tumor."

"What we're doing is taking a lot of evolution that enabled Listeria to infect human immune systems, and an equal amount of evolution that enables humans to get rid of Listeria once this occurs. We are then co-opting and redirecting all of these complex immune responses and targeting them against cancer," Rothman said.

The researchers divided the patients into three groups of five; each group received two doses of either 1x109, 3.3x109 or 1x1010 units of Listeria at three-week intervals. They administered ampicillin five days after each dose, first intravenously and then orally for 10 days.

Each patient developed flu-like symptoms, including fever, chills and nausea with or without vomiting. In the lower doses, these symptoms were treated with non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) and anti-emetics. Patients in the highest dose group had the same but more severe symptoms.

Rothman used the RECIST criteria to assess the tumors in 13 patients. At the end of the study, five patients had progression of their cancer, seven were stable, and one patient showed a partial response to the therapy. Three of the seven stable patients had tumor reductions of about 20 percent.

The partial response patient - who was stage IVb at trial initiation - was given six chemotherapy courses and a radical hysterectomy. Currently, she is tumor- free and her blood tests are normal. Six of the 13 patients are surviving, with a median survival of 424 days. Median survival for all 15 treated patients is 327 days.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Abstract 225

American Association for Cancer Research