T-Cell Therapy for Lymphoma Using Nonengineered Multiantigen-Targeted T Cells Is Safe and Produces Durable Clinical Effects

Spyridoula Vasileiou, Premal D. Lulla, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Wendy L. Callejas, Mrinalini Bilgi, Tao Wang, Mengfen J. Wu, Rammurti Kamble, Carlos A. Ramos, Rayne H. Rouce, Zihua Zeng, Adrian P. Gee, Bambi J. Grilley, Juan F. Vera, Catherine M. Bollard, Malcolm K. Brenner, Helen E. Heslop, Cliona M. RooneyAnn M. Leen, George Carrum

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

PURPOSE Patients with relapsed lymphomas often fail salvage therapies including high-dose chemotherapy and mono-antigen-specific T-cell therapies, highlighting the need for nontoxic, novel treatments. To that end, we clinically tested an autologous T-cell product that targets multiple tumor-associated antigens (TAAs) expressed by lymphomas with the intent of treating disease and preventing immune escape. PATIENTS AND METHODS We expanded polyclonal T cells reactive to five TAAs: PRAME, SSX2, MAGEA4, SURVIVIN, and NY-ESO-1. Products were administered to 32 patients with Hodgkin lymphomas (n 5 14) or non- Hodgkin lymphomas (n 5 18) in a two-part phase I clinical trial, where the objective of the first phase was to establish the safety of targeting all five TAAs (fixed dose, 0.5x107 cells/m2) simultaneously and the second stage was to establish the maximum tolerated dose. Patients had received a median of three prior lines of therapy and either were at high risk for relapse (adjuvant arm, n 5 17) or had chemorefractory disease (n 5 15) at enrollment. RESULTS Infusions were safe with no dose-limiting toxicities observed in either the antigen- or dose-escalation phases. Although the maximum tolerated dose was not reached, the maximum tested dose at which efficacy was observed (two infusions, 2x107 cells/m2) was determined as the recommended phase II dose. Of the patients with chemorefractory lymphomas, two (of seven) with Hodgkin lymphomas and four (of eight) with non-Hodgkin lymphomas achieved durable complete remissions (.xyears). CONCLUSION T cells targeting five TAAs and administered at doses of up to two infusions of 2x107 cells/m2 are well-tolerated by patients with lymphoma both as adjuvant and to treat chemorefractory lymphoma. Preliminary indicators of antilymphoma activity were seen in the chemorefractory cohort across both antigen- and doseescalation phases.

Original languageEnglish (US)
Pages (from-to)1415-1425
Number of pages11
JournalJournal of Clinical Oncology
Volume39
Issue number13
DOIs
StatePublished - May 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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