That comes with other indirect benefits: The T cells don’t get overstimulated or exhausted too quickly, and theoretically can function for longer, killing more cancer cells. They also just look more like the natural receptors immune cells use to bind to tumors, said von Hofe, mimicking the physiological interaction. “For each target we look at, essentially we’re cleaning them up,” he said. By tailoring an affinity level to each target based on its expression on normal cells, AffyImmune believes its tuning method draws that thin line for CAR-T cells to separate friend from foe. Rather, some of the weaker binders (which they describe as being in the nanomolar range) appeared to be better at eliminating tumors.īesides, these weaker binders would spare healthy cells with low expression of the target in favor of tumor cells, which tend to have much higher expression, said Eric von Hofe, president and COO. What they found was that the tightest binders, which have traditionally been favored, are not necessarily the best. When studying the interaction between an antigen called ICAM1 and its natural ligand, Moonsoo Jin and Gang Song tested multiple “affinity variants” - single chain monoclonal antibodies sporting different structures - against ICAM1. Tumor-specific antigens have been elusive. Programming the CAR-T cells to attack any cell bearing those tumor-associated antigens inevitably hurts normal cells, too. While hematological malignancies can be easily hunted down by markers like CD19 and BCMA (and clinicians can prevent side effects simply by wiping out B cells, the only other cell type expressing those antigens), it’s much harder to distinguish between solid tumor cells and organs. The issue underlying CAR-T’s toxicity problem has been well- documented. And it’s why Song’s team is handing over another $30 million to fund a first-in-human trial that kicked off late last year and send a second CAR-T therapy into the clinic. It was the reason why ORI, a Hong Kong-based healthcare VC firm focused on cancer, metabolic disorders and neurodegenerative diseases, decided to incubate a startup by the name of AffyImmune back in 2017.
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