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refractory to blinatumumab therapy,” June said today in response to an audience question.
CD19 therapies also represent the first wave of treatments from Kite Pharma (NASDAQ: KITE) of Los Angeles, which is working with Rosenberg’s team at NCI; and Juno of Seattle, which has exclusive license to programs from three academic centers: Memorial Sloan Kettering Cancer Center in New York City, the Fred Hutchinson Cancer Research Center in Seattle, and Seattle Children’s Research Institute.
As with CTL019, early results from the Kite and Juno programs have produced promising results in adults and children with refractory and relapsed acute lymphoblastic leukemia.
Side effects will of course remain a critical evaluation. But with no long-term safety red flags, so far, and a sense that the short-term side effects are manageable, investigators are working to expand the cell-based type of immunotherapy to new cancers.
For example, June told the audience that Penn has begun a pilot study of CTL019 in multiple myeloma, which was surprising because it’s not one of the cancers that’s known to produce CD19. At least not very much: June said that T cells, like the best canine detectives, can detect traces of CD19 too minute for human tests to detect. Might CD19-negative myeloma cells, which originate in CD19-positive B cells, still send enough of a signal to attract engineered T cells?
Rosenberg followed and devoted a good deal of his talk to the use of cell-based immunotherapy to treat solid tumors, a farther horizon but being explored by several groups. He elaborated upon a paper he and colleagues published this summer in the journal Clinical Cancer Research.
Their hypothesis is that solid tumors are much more driven by individual mutations than blood borne cancers; Rosenberg estimated only three or four percent of solid tumor mutations are common across people’s cancer. (The V600E BRAF mutation in melanoma is one example, which is why Plexxikon, now owned by Daiichi Sankyo, developed the drug vemurafinib (Zelboraf) for that specific patient subset.)
Personalized therapies will have to account for this heterogeneity, especially if they want to tackle the epithelial cancers, which account for 80 to 90 percent of all cancers. (They include lung, breast, prostate, and bowel cancers.)
“You’d need a new drug for every patient,” which sounds daunting until one surveys how far the field has already come in recent years, said Rosenberg.
Rosenberg and his colleagues think they’re already on the right track. They’ve been using T-cell receptor, or TCR, immunotherapy to treat melanoma with rousing success. (One difference between TCR and CAR: TCR cells penetrate tumor cells, while CAR cells attack the surface of the tumor. Here’s a very graphic picture Rosenberg showed during his talk of a horrendous melanoma that shrank to practically nothing in two months.)
But they didn’t exactly know how their TCR treatment worked. Melanoma has a lot more mutations than other cancers—“often by a factor of 10,” said Rosenberg—and they wanted to know which mutated antigens, or fragments of the tumor, among potentially hundreds were actually triggering the immune response.
They devised a new genetic screening method (dubbed tandem minigene library screening), using tissue from each patient, and identified the mutated antigen targets in each tissue sample. The screening process must be adapted to solid tumors with far fewer mutations than melanoma, but the minigene study brings the field “one step closer” to truly personalized cancer medicine, Rosenberg said.
Rosenberg’s group at NCI has a deep working relationship with Kite Pharma, which went public in June at $17 a share and has seen the price rise above $40. Kite funds trials conducted by NCI, and it has options to license the intellectual property developed during those trials. Kite founder and CEO Arie Belldegrun was once an NCI research fellow under Rosenberg.
With all that, though, Rosenberg is clear to state he’s not making any money from Kite’s progress. In fact, he turned the boilerplate disclaimer at the start of his talk into a joke. It also happened to serve as a telling comment about the current frenzy around immunotherapy: “Sadly, I have no personal financial disclosures to report.”