Cancer Vaccine Shows Benefit in Solid Tumors

Researchers recently reported that a cancer vaccine made by Celldex Therapeutics, Inc., of Hampton, NJ, was well tolerated in 45 patients with advanced solid tumors. Although the phase I trial was not designed to assess clinical benefit, the patients showed antibody and T-cell responses, suggesting that they might respond better to therapy with checkpoint inhibitors after vaccine treatment.

The vaccine, called CDX-1401, is designed to activate the immune system against cancers that express the tumor marker NY-ESO-1, which has been found in about 30% of melanomas and 10% to 20% of cases of non–small cell lung cancer, as well as in some other cancers. CDX-1401 consists of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 antigen.

Celldex is developing a companion diagnostic to identify patients most likely to benefit from the vaccine, says Tibor Keler, PhD, Celldex's chief scientific officer.

There are reasons to think CDX-1401 might succeed where other vaccines have failed, says Sacha Gnjatic, PhD, an immunologist who studies cancer vaccines at the Tisch Cancer Institute of the Icahn School of Medicine at Mount Sinai in New York, NY.

Gnjatic says NY-ESO-1 is a good target for therapy, because in normal adult tissue, it is only expressed in germ cells, but many solid tumors also express it.

To get an effective response to a tumor, a patient's immune system must react in three ways, Gnjatic explains: An effective immunotherapy must stimulate CD4 T cells, stimulate CD8 T cells, and release the brakes that prevent a robust immune response. So far, he says, CDX-1401 seems to have stimulated some CD4 T-cell responses and relatively weak CD8 T-cell responses.

Insofar as immune drugs work on their own in a small subset of patients, it's probably because the patient's body successfully fills in the missing parts of the triple punch, he says.

To get a broadly effective approach, patients will need help achieving all three—most likely with combination therapies, he notes.

Keler, a cancer biologist by training, agrees that combination therapies including vaccines may be useful treatments. Some of the participants in the recent trial, published in Science Translational Medicine, received CDX-1401 and then had treatment with checkpoint inhibitors such as ipilimumab or an experimental PD-1 pathway blocking agent, and experienced better-than-expected tumor response rates.

Keler says Celldex plans to test CDX-1401 in combination with its immune-modulating antibody, CDX-1127, a CD27 agonist that helps activate CD4 and CD8 T cells.

“From our perspective, vaccines will be a critical component of overall immunotherapy regimens,” he adds.

Side effects of the vaccine were minimal and are not expected to be greater than those of the checkpoint inhibitor alone, he notes.

Celldex is starting with NY-ESO-1, Keler says, but will eventually target other tumor antigens. “The technology we're developing here is really based on a platform,” he says. “We have other antigens we can use, and we can actually include more than one antigen with one vaccine.”