New targets for immunotherapy-based treatment of HPV-related cancers

This image shows HeLa cervical cancer cells stained for the cytoskeletal proteins actin (red) and tubulin (green). Cancer cells spread in the body with the help of mutated genes that drive changes in the cells' cytoskeleton -- the protein filaments and microtubules that control cell shape and contribute to cell movement.

Immunotherapies designed to treat cancers caused by the human papillomavirus (HPV), including cervical, anal and oropharyngeal cancers, have traditionally targeted protein antigens produced by the virus itself. However, such treatments have so far had little success in the regression of HPV-related cancers.

Now, in a study published April 14 in Science, scientists at the Center for Cancer Research and three other cancer research institutions show that immunotherapy treatments that resulted in complete regression of metastatic cervical cancer largely targeted two non-viral antigens.

In one of two patients in the study, 35 percent of the T cells in an immunotherapeutic infusion targeted mutant proteins called neoantigens, which are produced by cancerous cells.  In the second patient, 67 percent of the T cells targeted a single cancer germline antigen, which is commonly found in nearly half of all metastatic cervical cancers. In stark contrast, only 14 percent of the infused T cells targeted viral proteins.

The findings reveal the importance of considering nonviral antigen targets when designing effective immunotherapies for HPV-related cervical cancer. “This shifts the paradigm for the antigens to study and target in these viral cancers,” said Christian Hinrichs, M.D., an Investigator in the Experimental Transplantation and Immunology Branch and a lead author on the study.

The study also suggests that some patients may be treated with personalized, precision immunotherapies depending on whether their tumors express neoantigens or germline antigens. “We’re moving toward a gene engineering approach in which we can design defined antigen reactivity for each patient,” Hinrichs said.




Summary Posted: Sat, 04/01/2017