The CAR-T That Ignores CD19 On Purpose
The Wrong Target Works
PeproMene Bio and City of Hope built a CAR T-cell therapy that ignores the target every approved version is built around, and that turns out to be the point. CAR T-cell therapy takes a patient's own T cells, the immune system's killer cells, and re-engineers them in a lab to recognize one specific protein on the surface of their cancer, then puts the modified cells back into the bloodstream to hunt it down. The approved versions for B-cell lymphoma, the ones patients try first, all lock onto a protein called CD19. The trouble is that lymphoma cells that survive a round of CD19 CAR-T often survive by hiding the protein itself, a process doctors call antigen escape: the cancer comes back wearing a different face, and pointing the same weapon at the same spot does nothing. PeproMene's therapy, PMB-CT01, targets a different surface protein called BAFF-R, short for B-cell activating factor receptor, which most B-cell lymphomas keep making even after they have learned to duck CD19. The bet, led by City of Hope's Lihua E. Budde and PeproMene scientific founder Larry W. Kwak, was that a CAR-T aimed at a target the tumor never had to hide could put patients back into remission after the first CAR-T had already failed them.
Three Years Of Fragments
The evidence for that bet arrived in pieces before it arrived as a paper. City of Hope presented incremental results from PMB-CT01 at the American Society of Hematology's annual conference in 2023, 2024 and 2025, each year adding a handful more treated patients to a growing but still unpublished dataset. In December 2024 the International Follicular Lymphoma Innovation initiative committed up to $11 million specifically to push the BAFF-R approach forward in follicular lymphoma, a bet on a therapy that had not yet appeared in a peer-reviewed journal. The trial then expanded beyond its original home at City of Hope's Hematologic Malignancies Institute, run by Stephen Forman, to multiple additional US medical centers. The first patient treated in that expanded cohort had triple-hit high-grade B-cell lymphoma, a particularly aggressive subtype, and had already progressed after CD19 CAR-T. At the first assessment after infusion, that patient reached complete response: no detectable cancer. For a therapy that had spent three years as a conference abstract, an expansion-cohort result that clean was the sign the effect might not be a fluke of the original small group.
The Lancet Makes It Formal
On September 8, 2026, The Lancet published the trial's results as a peer-reviewed research letter, the first time the data had appeared outside a conference slide. Seven of the nine patients treated reached complete response, and four of six who had already failed CD19 CAR-T before PMB-CT01 put them into remission. Every complete response was still holding at data cutoff, with no relapses, and the longest has now lasted 35 months. Every case of cytokine release syndrome, the flu-like immune overreaction CAR-T therapies commonly trigger, graded mild, and the two reported cases of ICANS, the neurotoxicity that can follow CAR-T and sometimes causes confusion or seizures, also graded mild. That is a gentler profile than typically reported for the approved CD19 products. None of that erases the caveats a nine-patient trial carries by definition. A research letter is a shorter, faster format than a full Lancet paper, this is a single-arm Phase 1 with no comparison group, and seven of nine is a fraction small enough that one more relapse would move the headline number by more than ten points. The patients this actually reaches are the ones oncologists currently have almost nothing left to offer: people whose lymphoma has already outrun the standard CAR-T option, for whom a second real therapy, not just a case report, was until this month largely theoretical.
On September 8, 2026, The Lancet published PMB-CT01's trial results as a peer-reviewed research letter, adding seven complete responses out of nine patients to data that had previously existed only across three years of ASH conference slides. PMB-CT01 is still a nine-patient Phase 1, and expansion cohorts often erode a small trial's best numbers before they confirm them. But the trial is now enrolling at multiple US sites beyond City of Hope, and the next real test is named: whether the complete response rate holds once the expansion cohort reaches its next reported readout.
Sources
- PeproMene Bio's release with full trial results, safety data and funding history (prnewswire.com)
- BioSpace confirms trial expansion, named investigators, expansion-cohort result (biospace.com)
- PubMed indexes the Lancet research letter with named authors (pubmed.ncbi.nlm.nih.gov)
- ASH / Blood prior conference abstracts (2023-2025) (ashpublications.org)