Friday, December 7, 2012

Vijaya Joshi’s ultimate goal is to develop an effective vaccine for cancer. Along the way, the little details mean a lot.

“It’s not just about the big picture of treating cancer,” says Joshi, a Ph.D. candidate in pharmaceutics and translational therapeutics. “We start with putting together some molecules in a compatible formulation and then work towards carefully testing its activity against cancer. Every small step becomes important.”

Joshi studies size dependency of poly(lactide-co-glycolide) particles, also called PLGA, in generating antigen-specific immune responses. She works to develop vaccines, focusing specifically on creating delivery systems that enhance vaccine efficacy.

When a cell is cancerous, some of the protein molecules can undergo mutations or be expressed in higher concentrations than in non-cancerous cells. In the lab, Joshi is using these tumor-specific proteins to make a cancer vaccine.

“We change the overall efficacy of the immune response to a tumor-specific protein by attaching it to immunostimulatory bacterial DNA,” says Joshi. “We can also improve the anti-tumor immune response by delivering tumor-specific proteins in polymeric particulate based delivery systems.”

The tumor-specific protein is then injected back into a mouse and, if all goes according to design, immunity is stimulated against cancer. “Ultimately, the goal is when a subset of these immune cells, such as cytotoxic T lymphocytes are activated against a specific tumor protein,” says Joshi, “they will survey and kill any cancerous cell expressing the aforementioned protein.”

She is researching size-dependent uptake (or absorption rate) of polymer particles carrying tumor-specific proteins and the ability of these particles to stimulate tumor-specific immunity. The larger the polymer particle, the more proteins it can carry. However, larger polymer particles are more difficult for cells to absorb. Joshi’s challenge is to find the right combination of small size, maximum cargo space, and quick cargo release. She wants to find the largest polymer particle that cells can readily absorb in order to deliver the most proteins to stimulate tumor immunity.

Finding this balance is a lengthy, painstaking process involving many steps in the research lab.

The effort is worthwhile. Joshi’s mentor, Professor Aliasager Salem, says that research focused on improving the efficacy of vaccines has the potential to be translated into the clinic.

“And if it is translated into the clinic,” says Salem, “it will have a significant impact on anybody that needs vaccinations.”

Salem also notes that any proprietary technology that comes out of the lab as a result of her research will provide an economic benefit for the state of Iowa, as well.

Professor Salem praises Joshi’s work ethic, perseverance, skill, and passion for her research.

“She has a very strong pharmaceutical sciences background that bridges the immunology and the basic science particle fabrication components of her project,” says Salem. “She works well at the interface of the chemistry and biology.”

Joshi credits Salem and other departmental faculty, who have taught her about the technical aspects of developing drug delivery systems.

Joshi says she was drawn to Salem’s lab because it enabled her to use her undergraduate background in pharmacy toward treating cancer. “It is a perfect opportunity to integrate my expertise in formulation development and my desire to contribute towards our fight against cancer,” says Joshi.

Through immunotherapy breakthroughs, Joshi hopes cancer patients might avoid the side effects of radiation and chemotherapy treatments.

“I don’t claim we will develop something overnight or claim we can treat every kind of cancer, but I’m very proud of what I’m doing,” says Joshi. “I’m very proud that I am utilizing all these years of study to work toward development of some great new therapy that can help people.”

During the summer of 2012, Joshi interned at biotechnology company Genentech, located in San Francisco. She says the internship gave her an illuminating look at the other end of the process.

“I actually talked to people involved in designing phase-one clinical trials,” says Joshi. “I worked with the nitty gritty details of making sure the formulation was perfect. You must make sure you have ironed out everything before you put your formulation into the clinics.”

“I think this will probably help me. Taking what we make in the lab to the FDA is not an easy process. This experience gave me an idea of what we need to do experimentally so we have a strong case to put in front of the FDA.”