In their experiments with mice, the researchers found that a 10-fold dose of the conjugate in a week, or 100-fold dose of IR700 by itself "did not cause any acute and sub-acute side effects," Kobayashi notes, adding that "all free or catabolized IR or IR700-amino acids were excreted into urine very quickly, over 97 percent within a day." He adds that they have no concerns in terms of toxicity related to PIT, as "no toxicity was shown with this dose of constant wave or 10-fold bright pulse light." The largest side effect noted, he says, was that mouse body temperature did increase when the mice were exposed to maximum light to their entire bodies. Several mice did die due to crash syndrome when large tumors were treated, which Kobayashi says was due to too many cancer cells crashing within a minute, releasing potassium and leading to heart arrest. The therapy should be slowed down to eliminate this problem, he says.
There are several steps ahead of them to advance this therapy, Kobayashi explains, starting with trying to determine "the best regimen of combining PIT for dosing MAb-IR700 and timing/dose of shining [near-infrared] light."
"We now know immediate cell crash by PIT can promote the MAb-IR700 reach to the deep-sitting hidden cancer cell, and second dose of light can clear these remnant cells," says Kobayashi.
The researchers will also work to establish a monitoring method to evaluate the immediate effects of PIT. PIT can crash 99 percent of cancer cells within 10 to 15 minutes, he notes, but tumor size stays the same before the cell debris is cleaned up by microphages. As such, they will work to find a diagnosis method to ensure all cancer cells crash.
"We believe this PIT method is already mature enough to apply to the clinical trial," says Kobayashi. "We [will] try to make a GMP compound for proceeding PIT to the clinical trial."
