Seeking a vaccine to prevent breast cancer's return
by Will SansonThe surgery has gone well and the patient is in recovery. Now come the six words that comfort the families of cancer patients - "We think we got it all." But cancer is a relentless disease. After surgery, the next line of defense is "adjuvant" or follow-up therapy such as chemotherapy, hormone therapy or radiation. Even with the best surgery and follow-up, no one can guarantee that the cancer is gone for good. But what if there were a vaccine to guarantee against recurrence?
Claudia Gravekamp, Ph.D., assistant professor in the department of cellular and structural biology at the Health Science Center, and her research group have spent the past three years working on vaccines for childhood cancer and breast cancer. One vaccine reduces tumor growth by 50 percent in mice with neuroblastoma, a childhood cancer that spreads through the abdomen. Another vaccine, even more eye-catching, appears to stop recurrent breast cancer in its tracks. "We were able to eliminate breast metastases almost completely with this vaccine in a mouse breast tumor model," Dr. Gravekamp said. Metastases are tumors that spread to other parts of the body from an original tumor.
The vaccines work by producing antigens, which are substances (such as proteins) that stimulate an immune response. The antigens activate immune system T-cells that recognize tumor cells (the T-cells are sort of like police dogs trained to sniff out illegal narcotics). The beauty of the vaccine approach is that it is specific - the neuroblastoma vaccine produces an antigen that sounds the alarm to T-cells to destroy only neuroblastoma, not surrounding healthy tissue.
The breast cancer vaccine is exciting because it mimics, in a mouse model, the action of an antigen that "has been detected in many human breast tumor biopsies but not in normal tissues," Dr. Gravekamp said. The vaccine produces a mouse antigen that triggers the T-cell "police dogs" to sniff out the spreading breast cancer and destroy it.
For the breast cancer experiment, Dr. Gravekamp studied two groups of 15 mice each. One group of mice received the vaccine that makes the antigen, while the other group did not. Two weeks after immunization, the mice were injected with a tumor cell line that generates a breast tumor and metastases. Four weeks later, six of the mice in the control group developed metastases at the surface of the liver, lungs, diaphragm and other sites. In comparison, only one of the 15 vaccine-treated mice had a cancer recurrence.
The experiment is encouraging, considering the stubborn nature of recurrent breast cancer. "Metastatic breast cancer is still not very amenable to therapy,"
Dr. Gravekamp said. "While most solid tumor is removed by surgery, the problem is that cells remain to metastasize. Vaccines that control metastatic disease may be useful as an adjunctive therapy to surgery or conventional chemotherapy in breast cancer management." San Antonioís Cancer Therapy and Research Center (CTRC) funded her projects, along with the American Federation for Aging Research (AFAR), the National Institute on Aging (NIA) and the Childrenís Cancer Research Institute (CCRI), all of which supported the development of cancer vaccines and new mouse models. Dr. Gravekamp is a past recipient of the Barbara H. Bowman, Ph.D., Award in Cancer Prevention Research from the San Antonio Cancer Institute, a partnership of the Health Science Center and the CTRC. Her laboratory team includes postdoctoral fellow Roza Sypniewska, Ph.D., and senior research assistant Melissa Tarango, M.S.
Another project of Dr. Gravekampís team involves development of mouse models for studying cancer formation in different age groups. The NIA views the research as groundbreaking. "Aged individuals do not respond to immunization or chemotherapy in exactly the same ways young individuals respond," said Nancy L. Nadon, Ph.D., head of the NIAís Office of Biological Resources and Resource Development. "Dr. Gravekampís work todevelop an inducible model of breast cancer in the mouse is an important step for developing vaccines and cancer treatments optimized for the patientís age.†These mouse models will also be useful tools for investigating the progression of cancer in individuals at different ages, allowing investigations to tease out age-related factors in cancer development and treatment."
"The idea that tumor-specific immunity might vary with age is an important one to test, and the concept of vaccine treatment is attractive because of potentially lower toxicity with this form of therapy," said Odette Van Der Willik, director of grant programs for AFAR. "Dr. Gravekamp is a well-trained investigator with specific expertise in the vaccine area, and because this project was a new area of investigation for her, AFAR hoped that by providing support for her project, this would further stimulate and increase her research efforts in this area."
Dr. Gravekamp hopes to develop multi-antigen vaccines. Because tumors are genetically unstable, a truly effective vaccine will produce enough antigens to awaken more than one tumor-sniffing T-cell.
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