A Second CAR-T Target Rescues Relapsed Patients
A Different Door In
Stephen Forman's team at City of Hope set out to answer a specific problem: what do you do for a lymphoma patient whose CAR-T therapy already failed once. Standard CD19 CAR-T works by taking a patient's own T cells, engineering them to recognize CD19, a protein studding the surface of B cells including the cancerous ones, and infusing them back in as a living drug. It cures a meaningful share of patients. But 30 to 60 percent relapse, often because the tumor simply stops making CD19, a disappearing target the engineered T cells can no longer see. Forman's group, working with a therapy whose scientific founder is Larry Kwak, tried a different receptor instead: BAFF-R, the docking site B cells use to receive a survival signal called BAFF, without which they die. A cancerous B cell can shed CD19 and keep living. Shedding BAFF-R is a harder trade, because the same marker the immune therapy is hunting is also the signal keeping the cell alive. Nine patients with relapsed or refractory B-cell lymphoma, six of whom had already gone through and failed standard CD19 CAR-T, received the new construct, called PMB-CT01, in a Phase 1 trial. Whether it would actually hold up in patients was still, going in, an open question.
Seven Out of Nine
Seven of the nine patients, 78 percent, reached complete response, meaning no detectable disease by the trial's imaging and lab criteria. Four of those seven were among the six 'CAR after CAR' patients, the ones for whom the field had, until now, few answers. Every complete response was still holding at last follow-up, the longest tracked patient now 35 months out from treatment, nearly three years with no cancer detected after a therapy that had already failed them once. The safety data reads almost as notable as the efficacy: every case of cytokine release syndrome and neurotoxicity, the two dangerous inflammatory reactions CAR-T is known for, stayed at Grade 1, the mildest classification, a lighter toxicity signal than what's typically reported for the four FDA-approved CD19 products, Kymriah, Yescarta, Tecartus and Breyanzi. The results appeared as a research letter in The Lancet on September 8, a shorter, faster format meant to get real findings in front of other researchers before a full manuscript is ready, and that distinction matters for what you can actually conclude. Nine patients in one arm, no comparison group, no randomization: my read is that this establishes BAFF-R CAR-T can produce durable remissions in a small group, not that it beats or even matches CD19 CAR-T at scale. The company's own language reaches for 'breakthrough' and 'likelihood of cure.' The data itself shows four of six previously CAR-T-failed patients, plus three more, in complete response at up to 35 months of follow-up.
Who's Paying For This
The capital behind PMB-CT01 is unusual for cell therapy. PeproMene Bio raised a $40.2 million Series B, standard biotech financing, but the more interesting check came in December 2024: up to $11 million from the Institute for Follicular Lymphoma Innovation, a patient-advocacy nonprofit that runs what it calls venture philanthropy, meaning it puts foundation money directly into one company's single drug candidate rather than spreading bets across a portfolio the way a normal VC fund would. Follicular lymphoma and its relapsed-CAR-T subset are too narrow for a fund chasing blockbuster returns, which is why mainstream capital passed. A disease foundation stepping into that gap is good news for the patients it represents, and a nonprofit funder now holds a direct financial stake in one company's pricing and access decisions, a different animal from one that only funds independent academic research. The roughly one-third to one-half of every CD19 CAR-T cohort who relapse are the patients who feel this first, a population that until this month had, per the approved drug labels, no CAR-T retreatment option at all. Existing CAR-T products already list at $373,000 to $537,600 a dose before hospitalization. Nothing in the Lancet letter says what a BAFF-R retreatment would cost, only that City of Hope's own trial has now expanded from a single site to multiple U.S. locations.
What The Lancet actually published is nine patients, one arm, no control, and a 35-month ceiling on how long anyone has been watched. No multi-site data yet, no control arm, 35-month max follow-up: BAFF-R gave four patients whose first CAR-T failed a working alternative that didn't used to exist. Whether that holds at multiple sites and larger numbers is now a question for the multi-site expansion already underway at City of Hope.
Sources
- PR Newswire -- PeproMene Bio's release detailing the Lancet publication, trial numbers and safety data (prnewswire.com)
- BioSpace -- mirrored company release with trial and institutional detail (biospace.com)
- LA Business Journal -- $40.2 million Series B raise, per SEC filings (labusinessjournal.com)
- PeproMene Bio -- December 2024 announcement of IFLI's $11 million commitment (pepromenebio.com)
- IFLI -- nonprofit's mission and venture-philanthropy funding model (i-fli.org)
- KFF Health News -- pricing and insurer coverage of approved CAR-T therapies (kffhealthnews.org)