Experimental Cancer Vaccine Shrinks Tumors in Form of Non-Hodgkin Lymphoma

A preliminary study published this week in Nature Medicine could point to a new way of making immunotherapy effective in cancers that have proved resistant to treatment thus far.

Researchers have treated 11 patients with indolent non-Hodgkin lymphoma (iNHL) in an early phase study of a vaccine that is injected directly into tumors.

Typically, checkpoint blockade therapy doesn’t work in this type of cancer, and researchers have been looking for other ways to harness the immune system. Of the 11 patients who received the experimental vaccine, 6 experienced stable disease, 2 had partial remission, and 1 had a complete remission.

The concept recognizes that for some reason, T-cells that are the foundation of the checkpoint blockade revolution don’t seem to recognize iNHL. But if given help from a messenger of the immune system—dendritic cells—the combination might attack cancer ferociously.

According to the authors, the treatment regimen for the 11 patients involved the following:

• A human protein form of FMS-like tyrosine kinase-3 ligand (FLT3L).
• Radiotherapy
• A TLR3 agonist

This process acts to stimulate the dendritic cells; it would be expected that if used with a checkpoint inhibitor, antigens created during radiation would be carried dendritic cells to T-cells. The authors reported that patients who had a response developed a population of PD-1 CD8 T-cells after the vaccine regimen, “prompting a follow-up trial of the combined therapy.”

Researchers also gave the vaccine in combination with checkpoint blockade therapy to mice. When the mice with iNHL were given checkpoint blockade therapy alone, it did not work. But the vaccine combination put 75% of the mice into remission.

“The in situ vaccine approach has broad implications for multiple types of cancer,” lead author Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai said in a statement. “This method could also increase the success of other immunotherapies such as checkpoint blockade.”

The results were good enough that the team at Mount Sinai has started a clinical trial to try the 3-step vaccine in other cancers, including squamous head and neck cancers.

The investigators are collaborating with Celldex Therapeutics and Merck, according to clinicaltrials.gov.

Reference

Hammerich L, Marron TU, Upadhyay R, et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination [published online April 8, 2019]. Nature Med. 2019; doi: 10.1038/s41591-019-0410-x.