March 27, 2015
By Riley McDermid, BioSpace.com Breaking News Sr. Editor
Wall Street analysts who attended the 5th Annual Cancer Immunotherapy: A Long-Awaited Reality conference came away feeling that the emergence of checkpoint inhibitors and CAR-T over the last several years is only the tip of the iceberg for immunotherapy, said Boris Peaker, a biotech analyst with Cowen and Company in a note Friday.
Peaker said there was “plenty of discussion” around checkpoint inhibitors, with the keynote speaker noting that there hasn’t been an indication/histology that hasn’t responded to anti-PD-1/PD-L1 therapy.
“There was lots of focus on finding biomarkers to predict responders, understanding why patients fail anti-PD-1/PD-L1 therapy, and what other agents will best complement PD-1/PD-L1 agents,” wrote Peaker in a note to investors. “Numerous panelists noted that mutational load and quantity of tumor infiltrating lymphocytes have shown to correlate somewhat with response, but conceded that better approaches were needed.”
Peaker also noted the concern from attendees about converting patients with poor T-cell infiltrate into T-cell inflamed tumors to sensitize to PD-1 blockade. “Panelists also noted that while CTLA-4, PD-1, PD-L1 are currently the primary focus of checkpoint inhibitor therapy, there are 100s of other targets (co-stimulatory and co-inhibitory) within the T-cell checkpoint pathway and that many more viable targets will emerge,” said Peaker.
Above all, however, CAR-T therapies captured the spotlight yet again. There were two main areas of focus surrounding CAR-T cell discussions which included improving the current CD19 CAR-Ts and identifying suitable antigens for solid tumors.
One presentation spoke to the poor response rates that have been observed in CLL compared to ALL. One reason might be the tumor microenvironment of CLL, “specifically regulatory T-cells,” said Peaker.
“One presentation discussed the next generation of CAR-T cells that will be constructed to express the CAR/TCR, as well as the IL-12 cytokine to modify the tumor microenvironment. In regards to solid tumor antigens, there was a clear consensus among panelists that there was no CD19-like antigen at the moment.”
One big surprise from the conference? The bandwidth devoted to vaccines.
“There was a large amount of time spent discussing vaccines (more than we expected). Many panelists noted that while vaccines have fallen out of favor because of past failures, the emergence of checkpoint inhibitors should give vaccines a second life,” note Peaker.
“One panelist, however, said that if vaccines want to re-emerge they first need to demonstrate that they can rescue checkpoint inhibitor failures,” he said. “Several presentations discussed the possibility of generating in-situ vaccines using TLR9 agonists for antigen release and Flt3-l to enhance dendritic cell function. Most panelists agreed that the adjuvant setting represented the best place to study vaccines.”
