Vaccine helps T cells target tumors
BY Bryan Tutt
October 07, 2015
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on October 07, 2015
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¨Cspecific 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¨Cpositive 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.