Vaccine helps T cells target tumors

A vaccine that delivers an antigen to dendritic cells, in turn activating killer T cells that can target specific cancers, is being investigated in two ongoing clinical trials.

The first trial began enrolling patients with locally advanced or metastatic sarcoma, melanoma, ovarian cancer, non-small cell lung cancer, or breast cancer last year. To be eligible, patients’ biopsies had to show NY-ESO-1 expression in at least 5% of tumor cells. Another eligibility requirement was low tumor burden.

“Patients with bulky or rapidly progressing disease might be immunosuppressed and might not be able to generate an immune response fast enough to see a benefit from the vaccine as a single agent,” said Neeta Somaiah, M.D., principal investigator representing MD Anderson in the multi-institutional trial.

Patients received three or four injections of the vaccine LV305, given at three-week intervals, with the dose escalating each time.

The vaccine is a lentiviral gene vector that specifically binds to dendritic cells in a patient’s body via surface receptor CD209 and introduces the full length of the NY-ESO-1 antigen into these cells. The dendritic cells then present the antigen to CD8-positive T lymphocytes via the major histocompatibility class I molecules on the cell surface. The activated CD8+ cells can then recognize and attack cancer cells that express NYESO-1.

After treatment with the vaccine, eight of the 12 patients injected had stable disease at last follow-up and one patient had tumor regression of about 14%.

“The clinical and immunological response data are encouraging and warrant further study,” Somaiah said.

The second trial is now enrolling patients with sarcoma, melanoma, non-small cell lung cancer, and ovarian cancer. Patients will be given LV305 sequentially with G305. The sequential use of LV305 and G305 is designed to produce NY-ESO-1–specific CD8+ cell, CD4+ cell, and antibody responses.

The eligibility requirements of the CMB305 trial are similar to those of the LV305 monotherapy trial.

Future studies may combine CMB305 with a programmed cell death 1 (PD-1) inhibitor in patients with NY-ESO-1–positive tumors.

“Our early results show that LV305 is safe and generates an immune response,” Somaiah said. “Future studies will determine the best combination and sequence of agents to generate an effective and durable immune response with a robust antitumor effect.”

This story originally appeared in the August 2015 issue of OncoLog. Read it in its entirety here.