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Hydrogel Recruits Immune Cells To Improve Cancer Vaccine Effectiveness

Bioengineering: Treatment strategy could improve the performance of existing cancer vaccines by priming the immune system

by Leigh Krietsch Boerner
September 30, 2014

Schematic of a strategy for boosting effectiveness of a cancer vaccine.
Credit: Biomacromolecules
Researchers tested a new strategy to increase the effectiveness of cancer vaccines in mice. They inject mice with a hydrogel that releases a growth factor to recruit large numbers of dendritic cells to the site. The cells accumulate, and one week later, scientists inject a vaccine into the same site. The boost in dendritic cells increases the vaccine’s effectiveness.

Cancer vaccines can program the body’s own immune system to target and destroy tumor cells. Researchers have now found a simple way to prime the immune system for such vaccines: They use a hydrogel to attract large numbers of immune cells to the injection site, increasing the vaccine’s effectiveness (Biomacromolecules 2014, DOI: 10.1021/bm501166j).

Existing cancer vaccines are expensive and labor-intensive to administer. For example, one vaccine for prostate cancer approved by the Food & Drug Administration involves taking a patient’s own white blood cells, culturing them into immune cells called dendritic cells, exposing those cells to tumor antigens, and finally injecting the cells back into the patient. Dendritic cells are key players in activating an immune response against cancer. They patrol the body for foreign invaders, digest them, and then present antigens to killer T cells. The activated T cells circulate in the blood and attack tumor cells.

Pin Wang, a bioengineer at the University of Southern California, and his colleagues wanted to develop a cheaper and simpler approach. In particular, they wanted to avoid the need for transplanting cultured dendritic cells. First, the team synthesized a hydrogel from monomethoxypoly(ethylene glycol) and poly(lactic-co-glycolic acid) and then loaded it with a growth factor that attracts dendritic cells. Once injected, the hydrogel gradually breaks down and releases its payload, recruiting dendritic cells to the injection site. After about a week, the researchers inject the vaccine—consisting of a viral vector with tumor antigens—into the same site. With a lot of dendritic cells nearby, Wang and his team envisioned large numbers of tumor antigens reaching T cells.

To test the new strategy, the group first implanted melanoma tumors in mice and then injected the mice with an empty hydrogel or the hydrogel with the growth factor. Seven days later, the researchers administered the vaccine. They found that the mice that got the hydrogel with the growth factor had the smallest tumors after 30 days.

The method is very effective at attracting dendritic cells, says David J. Mooney, a bioengineer at Harvard University. This work symbolizes how immunologists are applying ideas from bioengineering and materials engineering, an approach that will be important in the future, he says.



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