Mike Hollan

Ho discusses how gamma-delta T cells can improve cancer treatments.
Pharmaceutical Executive: Can you provide some background on gamma-delta T-Cells?
William Ho: I’ve been in the biotech industry for over 22 years, and much of that was spent on the Wall Street side (investor banking, equity research, and as an investor). I co-founded the company together in 2016, and today we’re one of the leading companies developing gamma-delta T-Cells in oncology as a cellular therapy. Much of our work is based on Dr. Lamb’s lifetime of research on these t-cells. He was the first to describe them as being associated with better survival outcomes back in the 1990s.
They were first identified in the mid 1980s. Dr. Lamb spent the better part of 25 years or so trying to figure out how to make that observation into a therapeutic. He needed to figure out how to manufacture, scale, expand, and genetically engineer to enable the use in therapeutics.

PE: Can you go into recent developments with gamma-delta T-Cells?
Ho: Let’s take a quick step back. As I mentioned, I was a longtime investor at one of the leading healthcare VC funds running a portfolio in 2014 when the first Car-T companies became public. By 2019, I was convinced that this space was crowded, and I was trying to figure out how to go from targeting leukemias and lymphomas to treating solid tumor cancers with off the shelf therapies.
The gamma-delta T-Cells are unique subset of white blood cells that give them really attractive properties to get towards those off-the-shelf therapies for solid tumors. Early on, when people first developed Car-Ts, they focused on alpha-beta T-cells, partially because they’re easy to obtain. About 70% of all T-cell populations are made up of this type of T-cell, so I can take a blood sample and get a fairly high quantity of them and simply expand them to a therapeutic dose.
The early data was exciting. They were cures created and ten years later, patients are still without the cancers. The alpha-beta T-cells, however, are prone to toxicity and if we try to get towards the goal of donor derived or off-the-shelf therapies, there’s a chance that the infused cells would attack the patient’s body.
Since 2020, a lot of people were interesting developing different types of cells as Car-T and cell therapies that wouldn’t cause the same conditions and toxicities that we’ve seen with the alpha-beta cells.
The gamma-delta T-Cells are unique, because they sit between the alpha-beta cells and NK Cells. They have properties that allow them to kill directly, but they don’t require priming of the cells, don’t cause toxicities, and avoid other problems. These cells are partially memory-like, so there’s longer term persistence.
The challenge is that they are a minor subset of white blood cell. They only encompass about five percent of your total white blood cell population. To get therapeutic doses, we need to be able to expand them a lot more.

PE: Can these gamma-delta T-Cells only be used with solid tumor cancers?
Ho: No, they can be used in leukemias and lymphomas as well.
The advantages of the gamma-delta T-Cells are two-fold. First, one of their major functions is to distinguish between healthy and tumor cells. They don’t just wipe out everything that has its target, they specifically seek out leukemia cells and are able to leave healthy tissues alone.
The other is that one of the ways that tumors, whether they be leukemia or solid tumors, avoid the immune system is that they down-regulate certain markers on their surface. This allows the tumor to avoid the immune system, but the downregulation doesn’t block the gamma-delta T Cells ability to detect residual tu