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Updated: May 31, 2025
Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
HSP-CAR30 with a high proportion of less-differentiated T cells promotes durable responses in refractory CD30+
Ana Carolina Caballero1,2,3, Cristina Ujaldón-Miró1,2,3, Paula Pujol-Fernández1,2,3
1Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Abstract:
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).
Insights
A new CD30-directed chimeric antigen receptor T-cell therapy (CART30) shows promise for relapsed lymphoma. This enhanced therapy achieved a 100% response rate and durable remissions in a phase 1 trial.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor T-cell therapy targeting CD30 (CART30) has shown limited efficacy in relapsed/refractory CD30+ lymphomas.
- Durable responses remain a challenge in current CART30 treatments.
Purpose of the Study:
- To develop an enhanced CART30 cell product (HSP-CAR30) to improve efficacy and durability of responses.
- To evaluate the safety and efficacy of HSP-CAR30 in a phase 1 clinical trial for relapsed/refractory CD30+ lymphomas.
Main Methods:
- Developed HSP-CAR30 targeting a proximal CD30 epitope with modified ex vivo T-cell activation and addition of IL-21.
- Conducted a phase 1 clinical trial with 10 patients having relapsed/refractory classic Hodgkin lymphoma (HL) or CD30+ T-cell non-Hodgkin lymphoma.
- Analyzed T-cell composition, safety, response rates, and long-term durability.
Main Results:
- HSP-CAR30 product predominantly consisted of stem-like memory T cells (TSCM-like) and central memory T cells (TCM).
- The overall response rate was 100%, with 5 of 8 HL patients achieving complete remission (CR), and 60% maintaining ongoing CR after 34 months follow-up.
- No dose-limiting toxicities were observed; cytokine release syndrome was mild (grade 1) and no neurotoxicity occurred.
Conclusions:
- Targeting a proximal CD30 epitope and preserving less-differentiated memory T cells ex vivo may enhance CART30 efficacy.
- HSP-CAR30 demonstrates a favorable safety profile and high rates of durable complete remission in refractory CD30+ lymphomas.
- This approach offers a promising strategy for improving outcomes in patients with refractory HL.
