Typical allogeneic T-cell therapies for lymphoma often cause graft-versus-host disease (GVHD) and graft rejection. Researchers at the Center for Cell and Gene Therapy in Houston, Texas, have pioneered a unique virus-specific graft therapy to combat the alloreactive T-cell mediation that causes GVHD in these patients. They presented their results at the 64th American Society of Hematology Annual Meeting and Exposition.
Using Epstein-Barr virus-specific T cells (EBVSTs) modified with a CD30-targeting chimeric antigen receptor (CAR), David Quach, PhD, and his team treated patients with CD30+ lymphomas with escalating doses of CD30.CAR EBVST infusions (4 × 107 [DL1], 1 × 108 [DL2], or 4 × 108 [DL3]).
“To address GVHD, we are using [EBVSTs], which are virus-specific rather than allo-specific and have not produced GVHD in over 300 allogeneic recipients,” the researchers wrote.
A total of 14 patients with a median age of 36 years (range, 22-53 years) who had relapsed or refractory Hodgkin lymphoma underwent the study treatment with a median of 5 prior treatments (range, 3-6). Of the 14 patients who underwent treatment, none developed GVHD and 2 had reversible grade IV cytopenia.
Thirteen patients were evaluated per Lugano criteria and demonstrated an objective response rate of 69.2% overall. However, by Week 1 postinfusion, qPCR for the CD30.CAR transgene showed near background levels. The research team proposed 4 possible explanations for lack of transgene demonstrated in the analyzed samples.
“Possible explanations are that CD30.CAR EBVSTs: (1) Are eliminated by alloreactive T cells but persist sufficiently to eliminate tumors. (2) Can reactivate endogenous tumor-specific T cells that are responsible for the tumor responses. (3) Rapidly eliminate tumors and are then lost due to being intrinsically short-lived. (4) Become tissue resident at the tumor site.”
The researchers are pursuing these explanations further.
Having demonstrated that CD30.CAR EBVSTs can be a safe and effective treatment for these lymphomas and that the treatment may effectively prevent GVHD, the researchers wrote, “We now seek to improve the durability of responses and test whether CD30.CAR EBVST can be used as a platform for other ‘off-the-shelf’ CAR T-cell therapies.”
Quach DH, Ramos CA, Lulla PD, et al. CD30.CAR-modified Epstein-Barr virus-specific T cells (CD30.CAR EBVSTs) provide a safe and effective off-the-shelf therapy for patients with CD30-positive lymphoma. Abstract #167. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.