HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma

Jan 22, 2025Blood

Less-differentiated T cells in HSP-CAR30 help produce lasting responses in hard-to-treat CD30+ lymphoma

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Abstract

The overall response rate for HSP-CAR30 therapy in a phase 1 trial was 100% among 10 patients with relapsed/refractory classic Hodgkin lymphoma or CD30+ T-cell non-Hodgkin lymphoma.

HSP-CAR30 therapy resulted in complete remission in 5 of 8 patients with classic Hodgkin lymphoma.
An additional patient achieved complete remission after a second infusion of HSP-CAR30.
60% of patients maintained ongoing complete remission after a mean follow-up of 34 months.
The therapy was associated with a predominance of memory stem-like and central memory CAR30+ T cells (87.5% ± 5%).
No dose-limiting toxicities were observed, although 6 patients experienced grade 1 cytokine release syndrome.
CAR30+ T cells remained detectable in 3 of 5 evaluable patients at least 12 months post-infusion.

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CD30-directed chimeric antigen receptor T-cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, with a low proportion of durable responses. We have developed an academic CART30 cell product (HSP-CAR30) by combining strategies to improve performance. HSP-CAR30 targets a proximal epitope within the nonsoluble part of CD30, and the manufacturing process includes a modulation of ex vivo T-cell activation, as well as the addition of interleukin-21 (IL-21) to IL-7 and IL-15 to promote stemness of T cells. We translated HSP-CAR30 to a phase 1 clinical trial of 10 patients with relapsed/refractory classic Hodgkin lymphoma (HL) or CD30+ T-cell non-Hodgkin lymphoma. HSP-CAR30 was mainly composed of memory stem-like (TSCM-like) and central memory (TCM) CAR30+ T cells (87.5% ± 5%). No dose-limiting toxicities were detected. Six patients had grade 1 cytokine release syndrome, and no patient developed neurotoxicity. The overall response rate was 100%, and 5 of 8 patients with HL achieved complete remission (CR). An additional patient with HL achieved CR after a second HSP-CAR30 infusion. Remarkably, 60% of patients have ongoing CR after a mean follow-up of 34 months. CAR30+ T cells at expansion peak had a predominance of TSCM and TCM cells, and CAR30+ T cells remained detectable in 3 of 5 evaluable patients at least 12 months after infusion. Our study shows that selection of the epitope targeting CD30 and ex vivo preservation of less-differentiated memory T cells may enhance the efficacy of CART30 in patients with refractory HL. This trial is registered at www.clinicaltrials.gov (NCT04653649).

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HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+ lymphoma

Abstract

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